Marginal zone B cells: virtues of innate-like antibody-producing lymphocytes (original) (raw)

• Janeway, C. A. Jr & Medzhitov, R. Innate immune recognition. Annu. Rev. Immunol. 20, 197–216 (2002).
  CAS PubMed Google Scholar
• Cooper, M. D. & Alder, M. N. The evolution of adaptive immune systems. Cell 124, 815–822 (2006).
  Article CAS PubMed Google Scholar
• Bendelac, A., Bonneville, M. & Kearney, J. F. Autoreactivity by design: innate B and T lymphocytes. Nature Rev. Immunol. 1, 177–186 (2001).
  Article CAS Google Scholar
• Martin, F., Oliver, A. M. & Kearney, J. F. Marginal zone and B1 B cells unite in the early response against T-independent blood-borne particulate antigens. Immunity 14, 617–629 (2001).
  Article CAS PubMed Google Scholar
• Martin, F. & Kearney, J. F. Marginal-zone B cells. Nature Rev. Immunol. 2, 323–335 (2002). References 3 and 5 describe the function, ontogeny and reactivity of MZ B cells.
  CAS Google Scholar
• Treml, L. S. et al. TLR stimulation modifies BLyS receptor expression in follicular and marginal zone B cells. J. Immunol. 178, 7531–7539 (2007).
  Article CAS PubMed Google Scholar
• He, B. et al. The transmembrane activator TACI triggers immunoglobulin class switching by activating B cells through the adaptor MyD88. Nature Immunol. 11, 836–845 (2010). This was the first demonstration that BAFF and APRIL activate B cells through a signalling pathway involving the TLR-associated protein MYD88.
  Article CAS Google Scholar
• Pone, E. J. et al. BCR-signalling synergizes with TLR-signalling for induction of AID and immunoglobulin class-switching through the non-canonical NF-κB pathway. Nature Commun. 3, 767 (2012). This was the first demonstration that TI antigens trigger B cell activation and class switching by co-engaging BCRs and TLRs.
  Article CAS Google Scholar
• Mebius, R. E. & Kraal, G. Structure and function of the spleen. Nature Rev. Immunol. 5, 606–616 (2005). This article provides an overview of the structure, vascularization, cell composition and function of the spleen in mice and humans.
  CAS Google Scholar
• Chen, Y. et al. Defective microarchitecture of the spleen marginal zone and impaired response to a thymus-independent type 2 antigen in mice lacking scavenger receptors MARCO and SR-A. J. Immunol. 175, 8173–8180 (2005).
  Article CAS PubMed Google Scholar
• Kang, Y. S. et al. A dominant complement fixation pathway for pneumococcal polysaccharides initiated by SIGN-R1 interacting with C1q. Cell 125, 47–58 (2006). This work shows that MZ macrophages generate innate immune responses against encapsulated bacteria via an antibody-independent mechanism involving the uptake receptor SIGNR1 and an unusual complement activation pathway.
  Article CAS PubMed Google Scholar
• Bergtold, A., Desai, D. D., Gavhane, A. & Clynes, R. Cell surface recycling of internalized antigen permits dendritic cell priming of B cells. Immunity 23, 503–514 (2005).
  Article CAS PubMed Google Scholar
• Batista, F. D. & Harwood, N. E. The who, how and where of antigen presentation to B cells. Nature Rev. Immunol. 9, 15–27 (2009). This article provides an overview of the localization and mechanisms of antigen recognition by B cells.
  Article CAS Google Scholar
• Balázs, M., Martin, F., Zhou, T. & Kearney, J. F. Blood dendritic cells interact with splenic marginal zone B cells to initiate T-independent immune responses. Immunity 17, 341–352 (2002).
  Article PubMed Google Scholar
• Colino, J., Shen, Y. & Snapper, C. M. Dendritic cells pulsed with intact Streptococcus pneumoniae elicit both protein- and polysaccharide-specific immunoglobulin isotype responses in vivo through distinct mechanisms. J. Exp. Med. 195, 1–13 (2002). References 14 and 15 demonstrate that DCs interact with MZ B cells to induce antibody responses against blood-borne microorganisms.
  Article CAS PubMed PubMed Central Google Scholar
• Steiniger, B., Barth, P. & Hellinger, A. The perifollicular and marginal zones of the human splenic white pulp: do fibroblasts guide lymphocyte immigration? Am. J. Pathol. 159, 501–512 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Steiniger, B., Timphus, E. & Barth, P. The splenic marginal zone in humans and rodents: an enigmatic compartment and its inhabitants. Histochem. Cell Biol. 126, 641–648 (2006).
  Article CAS PubMed Google Scholar
• Puga, I. et al. B cell-helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen. Nature Immunol. 13, 170–180 (2012). This paper indicates that neutrophils provide unconventional help to human MZ B cells to generate antibodies specific for conserved microbial structures.
  Article CAS Google Scholar
• Spencer, J., Finn, T., Pulford, K. A., Mason, D. Y. & Isaacson, P. G. The human gut contains a novel population of B lymphocytes which resemble marginal zone cells. Clin. Exp. Immunol. 62, 607–612 (1985).
  CAS PubMed PubMed Central Google Scholar
• Tierens, A., Delabie, J., Michiels, L., Vandenberghe, P. & De Wolf-Peeters, C. Marginal-zone B cells in the human lymph node and spleen show somatic hypermutations and display clonal expansion. Blood 93, 226–234 (1999).
  CAS PubMed Google Scholar
• Dono, M. et al. Heterogeneity of tonsillar subepithelial B lymphocytes, the splenic marginal zone equivalents. J. Immunol. 164, 5596–5604 (2000).
  Article CAS PubMed Google Scholar
• Weill, J. C., Weller, S. & Reynaud, C. A. Human marginal zone B cells. Annu. Rev. Immunol. 27, 267–285 (2009). This article provides an updated overview of the differences between human and mouse MZ B cells.
  Article CAS PubMed Google Scholar
• Weller, S. et al. Human blood IgM “memory” B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire. Blood 104, 3647–3654 (2004). This was the first demonstration that MZ B cells recirculate in humans.
  Article CAS PubMed Google Scholar
• Berkowska, M. A. et al. Human memory B cells originate from three distinct germinal center-dependent and -independent maturation pathways. Blood 118, 2150–2158 (2011). This work provides molecular evidence that human MZ B cells are distinct from canonical memory B cells and may originate outside the germinal centre.
  Article CAS PubMed PubMed Central Google Scholar
• Guinamard, R., Okigaki, M., Schlessinger, J. & Ravetch, J. V. Absence of marginal zone B cells in Pyk-2-deficient mice defines their role in the humoral response. Nature Immunol. 1, 31–36 (2000). This work demonstrates the essential role of MZ B cells in early antibody responses to TI antigens in mice.
  Article CAS Google Scholar
• MacLennan, I. C. et al. Extrafollicular antibody responses. Immunol. Rev. 194, 8–18 (2003).
  Article CAS PubMed Google Scholar
• Amlot, P. L. & Hayes, A. E. Impaired human antibody response to the thymus-independent antigen, DNP-Ficoll, after splenectomy. Implications for post-splenectomy infections. Lancet 1, 1008–1011 (1985).
  Article CAS PubMed Google Scholar
• Kruetzmann, S. et al. Human immunoglobulin M memory B cells controlling Streptococcus pneumoniae infections are generated in the spleen. J. Exp. Med. 197, 939–945 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Castagnola, E. & Fioredda, F. Prevention of life-threatening infections due to encapsulated bacteria in children with hyposplenia or asplenia: a brief review of current recommendations for practical purposes. Eur. J. Haematol. 71, 319–326 (2003).
  Article PubMed Google Scholar
• Wasserstrom, H., Bussel, J., Lim, L. C. & Cunningham-Rundles, C. Memory B cells and pneumococcal antibody after splenectomy. J. Immunol. 181, 3684–3689 (2008).
  Article CAS PubMed Google Scholar
• Di Sabatino, A. et al. Depletion of immunoglobulin M memory B cells is associated with splenic hypofunction in inflammatory bowel disease. Am. J. Gastroenterol. 100, 1788–1795 (2005). References 27–31 indicate that human MZ B cells mediate protective antibody responses to encapsulated bacteria.
  Article CAS PubMed Google Scholar
• Traggiai, E. et al. Selective preservation of bone marrow mature recirculating but not marginal zone B cells in murine models of chronic inflammation. PLoS ONE 5, e11262 (2010).
  Article PubMed PubMed Central CAS Google Scholar
• Carsetti, R. et al. The loss of IgM memory B cells correlates with clinical disease in common variable immunodeficiency. J. Allergy Clin. Immunol. 115, 412–417 (2005).
  Article CAS PubMed Google Scholar
• Hart, M. et al. Loss of discrete memory B cell subsets is associated with impaired immunization responses in HIV-1 infection and may be a risk factor for invasive pneumococcal disease. J. Immunol. 178, 8212–8220 (2007).
  Article CAS PubMed Google Scholar
• Weller, S. et al. IgM+IgD+CD27+ B cells are markedly reduced in IRAK-4-, MyD88- and TIRAP- but not UNC-93B-deficient patients. Blood 120, 4992–5001 (2012). This was the first demonstration that the maintenance of human MZ B cells is highly dependent on signals from TLRs.
  Article CAS PubMed PubMed Central Google Scholar
• Pillai, S. & Cariappa, A. The follicular versus marginal zone B lymphocyte cell fate decision. Nature Rev. Immunol. 9, 767–777 (2009). This article provides an overview of the ontogeny of MZ B cells.
  Article CAS Google Scholar
• Szomolanyi-Tsuda, E. & Welsh, R. M. T-cell-independent antiviral antibody responses. Curr. Opin. Immunol. 10, 431–435 (1998).
  Article CAS PubMed Google Scholar
• Gatto, D., Ruedl, C., Odermatt, B. & Bachmann, M. F. Rapid response of marginal zone B cells to viral particles. J. Immunol. 173, 4308–4316 (2004).
  Article CAS PubMed Google Scholar
• Galili, U., Rachmilewitz, E. A., Peleg, A. & Flechner, I. A unique natural human IgG antibody with anti-α-galactosyl specificity. J. Exp. Med. 160, 1519–1531 (1984).
  Article CAS PubMed Google Scholar
• Ochsenbein, A. F. et al. Control of early viral and bacterial distribution and disease by natural antibodies. Science 286, 2156–2159 (1999).
  Article CAS PubMed Google Scholar
• Macpherson, A. J. & Harris, N. L. Interactions between commensal intestinal bacteria and the immune system. Nature Rev. Immunol. 4, 478–485 (2004).
  Article CAS Google Scholar
• Mazmanian, S. K., Liu, C. H., Tzianabos, A. O. & Kasper, D. L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122, 107–118 (2005).
  Article CAS PubMed Google Scholar
• Wei, B. et al. Resident enteric microbiota and CD8+ T cells shape the abundance of marginal zone B cells. Eur. J. Immunol. 38, 3411–3425 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Clarke, T. B. et al. Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nature Med. 16, 228–231 (2010). This was the first demonstration that molecules from the commensal microbiota enhance innate immunity after translocating from the intestine to the general circulation.
  Article CAS PubMed Google Scholar
• Lamouse-Smith, E. S., Tzeng, A. & Starnbach, M. N. The intestinal flora is required to support antibody responses to systemic immunization in infant and germ free mice. PLoS ONE 6, e27662 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Bos, N. A. et al. Serum immunoglobulin levels and naturally occurring antibodies against carbohydrate antigens in germ-free BALB/c mice fed chemically defined ultrafiltered diet. Eur. J. Immunol. 19, 2335–2339 (1989).
  Article CAS PubMed Google Scholar
• Butler, J. E. et al. Antibody repertoire development in fetal and neonatal piglets. II. Characterization of heavy chain complementarity-determining region 3 diversity in the developing fetus. J. Immunol. 165, 6999–7010 (2000).
  Article CAS PubMed Google Scholar
• Kool, J. et al. Detection of intestinal flora-derived bacterial antigen complexes in splenic macrophages of rats. J. Histochem. Cytochem. 42, 1435–1441 (1994).
  Article CAS PubMed Google Scholar
• Krueger, J. M. et al. Peptidoglycans as promoters of slow-wave sleep. II. Somnogenic and pyrogenic activities of some naturally occurring muramyl peptides; correlations with mass spectrometric structure determination. J. Biol. Chem. 259, 12659–12662 (1984).
  CAS PubMed Google Scholar
• Brenchley, J. M. et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nature Med. 12, 1365–1371 (2006).
  Article CAS PubMed Google Scholar
• Haas, A. et al. Systemic antibody responses to gut commensal bacteria during chronic HIV-1 infection. Gut 60, 1506–1519 (2011).
  Article CAS PubMed Google Scholar
• Chung, J. B., Silverman, M. & Monroe, J. G. Transitional B cells: step by step towards immune competence. Trends Immunol. 24, 343–349 (2003).
  Article CAS PubMed Google Scholar
• Mackay, F. & Schneider, P. Cracking the BAFF code. Nature Rev. Immunol. 9, 491–502 (2009).
  Article CAS Google Scholar
• Martin, F. & Kearney, J. F. Positive selection from newly formed to marginal zone B cells depends on the rate of clonal production, CD19, and btk. Immunity 12, 39–49 (2000).
  Article CAS PubMed Google Scholar
• Cariappa, A. et al. The follicular versus marginal zone B lymphocyte cell fate decision is regulated by Aiolos, Btk, and CD21. Immunity 14, 603–615 (2001).
  Article CAS PubMed Google Scholar
• Wen, L. et al. Evidence of marginal-zone B cell- positive selection in spleen. Immunity 23, 297–308 (2005).
  Article CAS PubMed Google Scholar
• Tanigaki, K. et al. Notch–RBP-J signaling is involved in cell fate determination of marginal zone B cells. Nature Immunol. 3, 443–450 (2002).
  Article CAS Google Scholar
• Hampel, F. et al. CD19-independent instruction of murine marginal zone B-cell development by constitutive Notch2 signaling. Blood 118, 6321–6331 (2011). References 54–58 show that signals from the BCR and NOTCH2 are important for the development of MZ B cells.
  Article CAS PubMed Google Scholar
• Scheeren, F. A. et al. T cell-independent development and induction of somatic hypermutation in human IgM+ IgD+ CD27+ B cells. J. Exp. Med. 205, 2033–2042 (2008). This works show that human MZ B cells develop during fetal life and undergo SHM through an antigen-independent process that does not require T cells.
  Article CAS PubMed PubMed Central Google Scholar
• Capolunghi, F. et al. CpG drives human transitional B cells to terminal differentiation and production of natural antibodies. J. Immunol. 180, 800–808 (2008).
  Article CAS PubMed Google Scholar
• Tsuiji, M. et al. A checkpoint for autoreactivity in human IgM+ memory B cell development. J. Exp. Med. 203, 393–400 (2006).
  Article PubMed PubMed Central Google Scholar
• Isnardi, I. et al. IRAK-4- and MyD88-dependent pathways are essential for the removal of developing autoreactive B cells in humans. Immunity 29, 746–757 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Cinamon, G. et al. Sphingosine 1-phosphate receptor 1 promotes B cell localization in the splenic marginal zone. Nature Immunol. 5, 713–720 (2004).
  Article CAS Google Scholar
• Cinamon, G., Zachariah, M. A., Lam, O. M., Foss, F. W. Jr & Cyster, J. G. Follicular shuttling of marginal zone B cells facilitates antigen transport. Nature Immunol. 9, 54–62 (2008).
  Article CAS Google Scholar
• Lu, T. T. & Cyster, J. G. Integrin-mediated long-term B cell retention in the splenic marginal zone. Science 297, 409–412 (2002). References 63–65 elucidate the mechanisms by which MZ B cells localize in the splenic MZ and transport antigens to the follicle.
  Article CAS PubMed Google Scholar
• Fukui, Y. et al. Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration. Nature 412, 826–831 (2001).
  Article CAS PubMed Google Scholar
• Croker, B. A. et al. The Rac2 guanosine triphosphatase regulates B lymphocyte antigen receptor responses and chemotaxis and is required for establishment of B-1a and marginal zone B lymphocytes. J. Immunol. 168, 3376–3386 (2002).
  Article CAS PubMed Google Scholar
• Rubtsov, A. et al. Lsc regulates marginal-zone B cell migration and adhesion and is required for the IgM T-dependent antibody response. Immunity 23, 527–538 (2005).
  Article CAS PubMed Google Scholar
• Karlsson, M. C. et al. Macrophages control the retention and trafficking of B lymphocytes in the splenic marginal zone. J. Exp. Med. 198, 333–340 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Dempsey, P. W., Allison, M. E., Akkaraju, S., Goodnow, C. C. & Fearon, D. T. C3d of complement as a molecular adjuvant: bridging innate and acquired immunity. Science 271, 348–350 (1996).
  Article CAS PubMed Google Scholar
• Test, S. T., Mitsuyoshi, J., Connolly, C. C. & Lucas, A. H. Increased immunogenicity and induction of class switching by conjugation of complement C3d to pneumococcal serotype 14 capsular polysaccharide. Infect. Immun. 69, 3031–3040 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Song, H. & Cerny, J. Functional heterogeneity of marginal zone B cells revealed by their ability to generate both early antibody-forming cells and germinal centers with hypermutation and memory in response to a T-dependent antigen. J. Exp. Med. 198, 1923–1935 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Chappell, C. P., Draves, K. E., Giltiay, N. V. & Clark, E. A. Extrafollicular B cell activation by marginal zone dendritic cells drives T cell-dependent antibody responses. J. Exp. Med. 209, 1825–1840 (2012). References 72 and 73 demonstrate that MZ B cells respond to protein antigens by following follicular or extrafollicular TD pathways.
  Article CAS PubMed PubMed Central Google Scholar
• Weller, S. et al. CD40–CD40L independent Ig gene hypermutation suggests a second B cell diversification pathway in humans. Proc. Natl Acad. Sci. USA 98, 1166–1170 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Weller, S. et al. Somatic diversification in the absence of antigen-driven responses is the hallmark of the IgM+ IgD+ CD27+ B cell repertoire in infants. J. Exp. Med. 205, 1331–1342 (2008). References 74 and 75 provide evidence that human MZ B cells undergo somatic diversification via a CD40-independent pathway that may not require antigens.
  Article CAS PubMed PubMed Central Google Scholar
• Genestier, L. et al. TLR agonists selectively promote terminal plasma cell differentiation of B cell subsets specialized in thymus-independent responses. J. Immunol. 178, 7779–7786 (2007).
  Article CAS PubMed Google Scholar
• Rubtsov, A. V. et al. TLR agonists promote marginal zone B cell activation and facilitate T-dependent IgM responses. J. Immunol. 180, 3882–3888 (2008).
  Article CAS PubMed Google Scholar
• Rawlings, D. J., Schwartz, M. A., Jackson, S. W. & Meyer-Bahlburg, A. Integration of B cell responses through Toll-like receptors and antigen receptors. Nature Rev. Immunol. 12, 282–294 (2012).
  Article CAS Google Scholar
• Belperron, A. A., Dailey, C. M. & Bockenstedt, L. K. Infection-induced marginal zone B cell production of _Borrelia hermsii_-specific antibody is impaired in the absence of CD1d. J. Immunol. 174, 5681–5686 (2005).
  Article CAS PubMed Google Scholar
• Haas, K. M., Poe, J. C. & Tedder, T. F. CD21/35 promotes protective immunity to Streptococcus pneumoniae through a complement-independent but CD19-dependent pathway that regulates PD-1 expression. J. Immunol. 183, 3661–3671 (2009).
  Article CAS PubMed Google Scholar
• Garcia de Vinuesa, C., O'Leary, P., Sze, D. M., Toellner, K. M. & MacLennan, I. C. T-independent type 2 antigens induce B cell proliferation in multiple splenic sites, but exponential growth is confined to extrafollicular foci. Eur. J. Immunol. 29, 1314–1323 (1999).
  Article CAS PubMed Google Scholar
• Timens, W., Boes, A. & Poppema, S. Human marginal zone B cells are not an activated B cell subset: strong expression of CD21 as a putative mediator for rapid B cell activation. Eur. J. Immunol. 19, 2163–2166 (1989).
  Article CAS PubMed Google Scholar
• Tangye, S. G., Liu, Y. J., Aversa, G., Phillips, J. H. & de Vries, J. E. Identification of functional human splenic memory B cells by expression of CD148 and CD27. J. Exp. Med. 188, 1691–1703 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Dunn-Walters, D. K., Isaacson, P. G. & Spencer, J. Analysis of mutations in immunoglobulin heavy chain variable region genes of microdissected marginal zone (MGZ) B cells suggests that the MGZ of human spleen is a reservoir of memory B cells. J. Exp. Med. 182, 559–566 (1995).
  Article CAS PubMed Google Scholar
• Klein, U., Rajewsky, K. & Kuppers, R. Human immunoglobulin (Ig)M+IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells. J. Exp. Med. 188, 1679–1689 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Seifert, M. & Kuppers, R. Molecular footprints of a germinal center derivation of human IgM+(IgD+)CD27+ B cells and the dynamics of memory B cell generation. J. Exp. Med. 206, 2659–2669 (2009). This work provides molecular evidence that human MZ B cells originate in a germinal centre reaction and may therefore be considered to be bona fide IgM+ memory B cells.
  Article CAS PubMed PubMed Central Google Scholar
• Tangye, S. G. & Good, K. L. Human IgM+CD27+ B cells: memory B cells or “memory” B cells? J. Immunol. 179, 13–19 (2007).
  Article CAS PubMed Google Scholar
• Kuraoka, M. et al. Activation-induced cytidine deaminase expression and activity in the absence of germinal centers: insights into hyper-IgM syndrome. J. Immunol. 183, 3237–3248 (2009).
  Article CAS PubMed Google Scholar
• Roll, P., Palanichamy, A., Kneitz, C., Dorner, T. & Tony, H. P. Regeneration of B cell subsets after transient B cell depletion using anti-CD20 antibodies in rheumatoid arthritis. Arthritis Rheum. 54, 2377–2386 (2006).
  Article CAS PubMed Google Scholar
• Carey, J. B., Moffatt-Blue, C. S., Watson, L. C., Gavin, A. L. & Feeney, A. J. Repertoire-based selection into the marginal zone compartment during B cell development. J. Exp.Med. 205, 2043–2052 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Swanson, C. L. et al. Type I IFN enhances follicular B cell contribution to the T cell-independent antibody response. J. Exp. Med. 207, 1485–1500 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Do, R. K. et al. Attenuation of apoptosis underlies B lymphocyte stimulator enhancement of humoral immune response. J. Exp. Med. 192, 953–964 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Oliver, A. M., Martin, F., Gartland, G. L., Carter, R. H. & Kearney, J. F. Marginal zone B cells exhibit unique activation, proliferative and immunoglobulin secretory responses. Eur. J. Immunol. 27, 2366–2374 (1997).
  Article CAS PubMed Google Scholar
• Mond, J. J., Lees, A. & Snapper, C. M. T cell-independent antigens type 2. Annu. Rev. Immunol. 13, 655–692 (1995).
  Article CAS PubMed Google Scholar
• Garcia De Vinuesa, C. et al. Dendritic cells associated with plasmablast survival. Eur. J. Immunol. 29, 3712–3721 (1999). Together with references 14 and 81, this work demonstrates that DCs enhance antibody responses to TI antigens by supporting the survival of extrafollicular plasmablasts derived from MZ B cells.
  Article CAS PubMed Google Scholar
• Litinskiy, M. B. et al. Antigen presenting cells induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nature Immunol. 3, 822–829 (2002).
  Article CAS Google Scholar
• Pack, M. et al. DEC-205/CD205+ dendritic cells are abundant in the white pulp of the human spleen, including the border region between the red and white pulp. Immunology 123, 438–446 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Ogembo, J. G. et al. SIRPα/CD172a and FHOD1 are unique markers of littoral cells, a recently evolved major cell population of red pulp of human spleen. J. Immunol. 188, 4496–4505 (2012).
  Article CAS PubMed Google Scholar
• Cols, M. et al. Stromal endothelial cells establish a bidirectional crosstalk with chronic lymphocytic leukemia cells through the TNF-related factors BAFF, APRIL, and CD40L. J. Immunol. 188, 6071–6083 (2012).
  Article CAS PubMed Google Scholar
• Xu, W. et al. Epithelial cells trigger frontline immunoglobulin class switching through a pathway regulated by the inhibitor SLPI. Nature Immunol. 8, 294–303 (2007).
  Article CAS Google Scholar
• He, B., Qiao, X. & Cerutti, A. CpG DNA induces IgG class switch DNA recombination by activating human B cells through an innate pathway that requires TLR9 and cooperates with IL-10. J. Immunol. 173, 4479–4491 (2004). References 96 and 99–101 show that BAFF and APRIL are produced by several innate cell types and induce CD40-independent class switching.
  Article CAS PubMed Google Scholar
• Groom, J. R. et al. BAFF and MyD88 signals promote a lupuslike disease independent of T cells. J. Exp. Med. 204, 1959–1971 (2007). This study provides an elegant demonstration that BAFF promotes antibody production through a mechanism involving the TLR-associated protein MYD88.
  Article CAS PubMed PubMed Central Google Scholar
• Castigli, E. et al. Transmembrane activator and calcium modulator and cyclophilin ligand interactor enhances CD40-driven plasma cell differentiation. J. Allergy Clin. Immunol. 120, 885–891 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Brodeur, S. R. et al. C4b-binding protein (C4BP) activates B cells through the CD40 receptor. Immunity 18, 837–848 (2003).
  Article CAS PubMed Google Scholar
• Li, S. et al. Rapidly induced, T-cell independent xenoantibody production is mediated by marginal zone B cells and requires help from NK cells. Blood 110, 3926–3935 (2007).
  Article CAS PubMed Google Scholar
• Leadbetter, E. A. et al. NK T cells provide lipid antigen-specific cognate help for B cells. Proc. Natl Acad. Sci. USA 105, 8339–8344 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Snapper, C. M. Mechanisms underlying in vivo polysaccharide-specific immunoglobulin responses to intact extracellular bacteria. Ann. NY Acad. Sci. 1253, 92–101 (2012).
  Article CAS PubMed Google Scholar
• Cunningham, A. F. et al. Salmonella induces a switched antibody response without germinal centers that impedes the extracellular spread of infection. J. Immunol. 178, 6200–6207 (2007).
  Article CAS PubMed Google Scholar
• Cobb, B. A., Wang, Q., Tzianabos, A. O. & Kasper, D. L. Polysaccharide processing and presentation by the MHCII pathway. Cell 117, 677–687 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Oliver, A. M., Martin, F. & Kearney, J. F. IgMhighCD21high lymphocytes enriched in the splenic marginal zone generate effector cells more rapidly than the bulk of follicular B cells. J. Immunol. 162, 7198–7207 (1999).
  CAS PubMed Google Scholar
• Attanavanich, K. & Kearney, J. F. Marginal zone, but not follicular B cells, are potent activators of naive CD4 T cells. J. Immunol. 172, 803–811 (2004).
  Article CAS PubMed Google Scholar
• Crotty, S. Follicular helper CD4 T cells (TFH). Annu. Rev. Immunol. 29, 621–663 (2011).
  Article CAS PubMed Google Scholar
• Idoyaga, J., Suda, N., Suda, K., Park, C. G. & Steinman, R. M. Antibody to Langerin/CD207 localizes large numbers of CD8α+ dendritic cells to the marginal zone of mouse spleen. Proc. Natl Acad. Sci. USA 106, 1524–1529 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Schmitt, N. et al. Human dendritic cells induce the differentiation of interleukin-21-producing T follicular helper-like cells through interleukin-12. Immunity 31, 158–169 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Bentebibel, S. E., Schmitt, N., Banchereau, J. & Ueno, H. Human tonsil B-cell lymphoma 6 (BCL6)-expressing CD4+ T-cell subset specialized for B-cell help outside germinal centers. Proc. Natl Acad. Sci. USA 108, E488–E497 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Barral, P. et al. B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in vivo. Proc. Natl Acad. Sci. USA 105, 8345–8350 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Bialecki, E. et al. Role of marginal zone B lymphocytes in invariant NKT cell activation. J. Immunol. 182, 6105–6113 (2009). Together with reference 106, references 116 and 117 indicate that MZ B cells undergo antibody production after interacting with iNKT cells.
  Article CAS PubMed Google Scholar
• De Santo, C. et al. Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A. Nature Immunol. 11, 1039–1046 (2010).
  Article CAS Google Scholar
• Hargreaves, D. C. et al. A coordinated change in chemokine responsiveness guides plasma cell movements. J. Exp. Med. 194, 45–56 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Ellyard, J. I., Avery, D. T., Mackay, C. R. & Tangye, S. G. Contribution of stromal cells to the migration, function and retention of plasma cells in human spleen: potential roles of CXCL12, IL-6 and CD54. Eur. J. Immunol. 35, 699–708 (2005).
  Article CAS PubMed Google Scholar
• Avery, D. T. et al. BAFF selectively enhances the survival of plasmablasts generated from human memory B cells. J. Clin. Invest. 112, 286–297 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• He, B. et al. Intestinal bacteria trigger T cell-independent immunoglobulin A2 class switching by inducing epithelial-cell secretion of the cytokine APRIL. Immunity 26, 812–826 (2007).
  Article CAS PubMed Google Scholar
• Lindh, E. et al. AIRE regulates T-cell-independent B-cell responses through BAFF. Proc. Natl Acad. Sci. USA 105, 18466–18471 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Jego, G. et al. Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. Immunity 19, 225–234 (2003).
  Article CAS PubMed Google Scholar
• Xu, W. et al. Macrophages induce differentiation of plasma cells through CXCL10/IP-10. J. Exp. Med. 209, 1813–1823 (2012). References 124 and 125 describe novel plasma cell differentiation pathways that involve an interplay between IL-6, type I IFNs and CXCL10.
  Article CAS PubMed PubMed Central Google Scholar
• Hendricks, J. et al. Class-switched marginal zone B cells in spleen have relatively low numbers of somatic mutations. Mol. Immunol. 48, 874–882 (2011).
  Article CAS PubMed Google Scholar
• Scapini, P. et al. G-CSF-stimulated neutrophils are a prominent source of functional BLyS. J. Exp. Med. 197, 297–302 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Crepaldi, L. et al. Up-regulation of IL-10R1 expression is required to render human neutrophils fully responsive to IL-10. J. Immunol. 167, 2312–2322 (2001).
  Article CAS PubMed Google Scholar
• Rauch, P. J. et al. Innate response activator B cells protect against microbial sepsis. Science 335, 597–601 (2012). This work demonstrates that a unique subset of innate B cells generates protection against sepsis by producing the pleiotropic cytokine GM-CSF.
  Article CAS PubMed PubMed Central Google Scholar
• Chu, V. T. et al. Eosinophils are required for the maintenance of plasma cells in the bone marrow. Nature Immunol. 12, 151–159 (2011).
  Article CAS Google Scholar
• Bernasconi, N. L., Traggiai, E. & Lanzavecchia, A. Maintenance of serological memory by polyclonal activation of human memory B cells. Science 298, 2199–2202 (2002). This work suggests that the long-lived survival of antibody-producing MZ and memory B cells is highly dependent on innate microbial signals.
  Article CAS PubMed Google Scholar
• Lande, R. et al. Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA–peptide complexes in systemic lupus erythematosus. Sci. Transl. Med. 3, 73ra19 (2011).
  Article PubMed PubMed Central Google Scholar
• He, B. et al. HIV-1 envelope triggers polyclonal Ig class switch recombination through a CD40-independent mechanism involving BAFF and C-type lectin receptors. J. Immunol. 176, 3931–3941 (2006).
  Article CAS PubMed Google Scholar
• Castigli, E. et al. TACI and BAFF-R mediate isotype switching in B cells. J. Exp. Med. 201, 35–39 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Kaminski, D. A. & Stavnezer, J. Enhanced IgA class switching in marginal zone and B1 B cells relative to follicular/B2 B cells. J. Immunol. 177, 6025–6029 (2006).
  Article CAS PubMed Google Scholar
• Le Bon, A. et al. Type I interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo. Immunity 14, 461–470 (2001).
  Article CAS PubMed Google Scholar
• Barral, P. et al. CD169+ macrophages present lipid antigens to mediate early activation of iNKT cells in lymph nodes. Nature Immunol. 11, 303–312 (2010).
  Article CAS Google Scholar
• Tarkowski, A. et al. Immunization of humans with polysaccharide vaccines induces systemic, predominantly polymeric IgA2-subclass antibody responses. J. Immunol. 144, 3770–3778 (1990).
  CAS PubMed Google Scholar
• Carson, P. J., Schut, R. L., Simpson, M. L., O'Brien, J. & Janoff, E. N. Antibody class and subclass responses to pneumococcal polysaccharides following immunization of human immunodeficiency virus-infected patients. J. Infect. Dis. 172, 340–345 (1995). References 122, 138 and 139 suggest that human IgG2 and IgA2 antibodies can be produced through TI pathways.
  Article CAS PubMed Google Scholar
• Dammers, P. M., de Boer, N. K., Deenen, G. J., Nieuwenhuis, P. & Kroese, F. G. The origin of marginal zone B cells in the rat. Eur. J. Immunol. 29, 1522–1531 (1999).
  Article CAS PubMed Google Scholar
• Toellner, K. M. et al. Low-level hypermutation in T cell-independent germinal centers compared with high mutation rates associated with T cell-dependent germinal centers. J. Exp. Med. 195, 383–389 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Herlands, R. A., Christensen, S. R., Sweet, R. A., Hershberg, U. & Shlomchik, M. J. T cell-independent and Toll-like receptor-dependent antigen-driven activation of autoreactive B cells. Immunity 29, 249–260 (2008). References 141 and 142 show that B cells can undergo SHM in a TI manner.
  Article CAS PubMed PubMed Central Google Scholar
• Lanning, D. K., Rhee, K. J. & Knight, K. L. Intestinal bacteria and development of the B-lymphocyte repertoire. Trends Immunol. 26, 419–425 (2005).
  Article CAS PubMed Google Scholar
• Mao, C. et al. T cell-independent somatic hypermutation in murine B cells with an immature phenotype. Immunity 20, 133–144 (2004).
  Article CAS PubMed Google Scholar
• Aranburu, A. et al. TLR ligation triggers somatic hypermutation in transitional B cells inducing the generation of IgM memory B cells. J. Immunol. 185, 7293–7301 (2010). References 144 and 145 provide additional evidence that some B cells activate the SHM machinery in response to innate signals without requiring T cells.
  Article CAS PubMed Google Scholar
• van de Pavert, S. A. & Mebius, R. E. New insights into the development of lymphoid tissues. Nature Rev. Immunol. 10, 664–674 (2010).
  Article CAS Google Scholar
• Zindl, C. L. et al. The lymphotoxin LTα1β2 controls postnatal and adult spleen marginal sinus vascular structure and function. Immunity 30, 408–420 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Mueller, S. N. & Germain, R. N. Stromal cell contributions to the homeostasis and functionality of the immune system. Nature Rev. Immunol. 9, 618–629 (2009).
  Article CAS Google Scholar
• Schneider, K. et al. Lymphotoxin-mediated crosstalk between B cells and splenic stroma promotes the initial type I interferon response to cytomegalovirus. Cell Host Microbe 3, 67–76 (2008).
  Article CAS PubMed PubMed Central Google Scholar