The double life of a B-1 cell: self-reactivity selects for protective effector functions (original) (raw)

• 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
• Haury, M. et al. The repertoire of serum IgM in normal mice is largely independent of external antigenic contact. Eur. J. Immunol. 27, 1557–1563 (1997).
  Article CAS PubMed Google Scholar
• Hooijkaas, H., Benner, R., Pleasants, J. R. & Wostmann, B. S. Isotypes and specificities of immunoglobulins produced by germ-free mice fed chemically defined ultrafiltered “antigen-free” diet. Eur. J. Immunol. 14, 1127–1130 (1984).
  Article CAS PubMed Google Scholar
• Andersson, J., Sjoberg, O. & Moller, G. Induction of immunoglobulin and antibody synthesis in vitro by lipopolysaccharides. Eur. J. Immunol. 2, 349–353 (1972).
  Article CAS PubMed Google Scholar
• Coutinho, A., Gronowicz, E. & Moller, G. Mechanism of B-cell activation and paralysis by thymus-independent antigens. Additive effects between NNP–LPS and LPS in the specific response to the hapten. Scand. J. Immunol. 4, 89–94 (1975).
  Article CAS PubMed Google Scholar
• Crampton, S. P., Voynova, E. & Bolland, S. Innate pathways to B-cell activation and tolerance. Ann. NY Acad. Sci. 1183, 58–68 (2010).
  Article CAS PubMed Google Scholar
• Bekeredjian-Ding, I. & Jego, G. Toll-like receptors — sentries in the B-cell response. Immunology 128, 311–323 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Meyer-Bahlburg, A. & Rawlings, D. J. B cell autonomous TLR signaling and autoimmunity. Autoimmun. Rev. 7, 313–316 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Li, X., Martin, F., Oliver, A. M., Kearney, J. F. & Carter, R. H. Antigen receptor proximal signaling in splenic B-2 cell subsets. J. Immunol. 166, 3122–3129 (2001).
  Article CAS PubMed Google Scholar
• Martin, F. & Kearney, J. F. B-cell subsets and the mature preimmune repertoire. Marginal zone and B1 B cells as part of a “natural immune memory”. Immunol. Rev. 175, 70–79 (2000).
  Article CAS PubMed Google Scholar
• Baumgarth, N., Tung, J. W. & Herzenberg, L. A. Inherent specificities in natural antibodies: a key to immune defense against pathogen invasion. Springer Semin. Immunopathol. 26, 347–362 (2005).
  Article CAS PubMed Google Scholar
• Bouvet, J.-P. & Dighiero, G. From natural polyreactive autoantibodies to a la carte monoreactive antibodies to infectious agents: is it a small world after all? Infect. Immun. 66, 1–4 (1998).
  CAS PubMed PubMed Central Google Scholar
• Stewart, J. Immunoglobulins did not arise in evolution to fight infection. Immunol. Today 13, 396–399 (1992).
  Article CAS PubMed Google Scholar
• Binder, C. J. & Silverman, G. J. Natural antibodies and the autoimmunity of atherosclerosis. Springer Semin. Immunopathol. 26, 385–404 (2005).
  Article CAS PubMed Google Scholar
• Duan, B. & Morel, L. Role of B-1a cells in autoimmunity. Autoimmun. Rev. 5, 403–408 (2006).
  Article CAS PubMed Google Scholar
• Hardy, R. R. B-1 B cells: development, selection, natural autoantibody and leukemia. Curr. Opin. Immunol. 18, 547–555 (2006).
  Article CAS PubMed Google Scholar
• Hayakawa, K., Hardy, R. R., Parks, D. R. & Herzenberg, L. A. The “Ly-1 B” cell subpopulation in normal immunodefective, and autoimmune mice. J. Exp. Med. 157, 202–218 (1983). This study makes a crucial connection between the increased IgM secretion that occurs in NZB/NZW mice owing to an aberrant population of CD5+ B cells and the natural IgM secretion by CD5+ B cells that occurs in normal mice.
  Article CAS PubMed Google Scholar
• Hayakawa, K., Hardy, R. R. & Herzenberg, L. A. Progenitors for Ly-1 B cells are distinct from progenitors for other B cells. J. Exp. Med. 161, 1554–1568 (1985). This study forms the basis for the 'lineage hypothesis' of B-1 cell development.
  Article CAS PubMed Google Scholar
• Kantor, A. B., Stall, A. M., Adams, S. & Herzenberg, L. A. Differential development of progenitor activity for three B-cell lineages. Proc. Natl Acad. Sci. USA 89, 3320–3324 (1992).
  Article CAS PubMed PubMed Central Google Scholar
• Kantor, A. B. The development and repertoire of B-1 cells (CD5 B cells). Immunol. Today 12, 389–391 (1991).
  Article CAS PubMed Google Scholar
• Godin, I. E., Garcia-Porrero, J. A., Coutinho, A., Dieterlen-Lievre, F. & Marcos, M. A. Para-aortic splanchnopleura from early mouse embryos contains B1a cell progenitors. Nature 364, 67–70 (1993). This study identified B cell precursors in the splanchnopleura region of mouse embryos that give rise only to B-1 cells after adoptive transfer.
  Article CAS PubMed Google Scholar
• Mizoguchi, A., Mizoguchi, E., Takedatsu, H., Blumberg, R. S. & Bhan, A. K. Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity 16, 219–230 (2002).
  Article CAS PubMed Google Scholar
• Yanaba, K. et al. A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity 28, 639–650 (2008).
  Article CAS PubMed Google Scholar
• Yang, M. et al. Novel function of B cell-activating factor in the induction of IL-10-producing regulatory B cells. J. Immunol. 184, 3321–3325 (2010).
  Article CAS PubMed 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
• Berland, R. & Wortis, H. H. Origins and functions of B-1 cells with notes on the role of CD5. Annu. Rev. Immunol. 20, 253–300 (2002).
  Article CAS PubMed Google Scholar
• Dorshkind, K. & Montecino-Rodriguez, E. Fetal B-cell lymphopoiesis and the emergence of B-1-cell potential. Nature Rev. Immunol. 7, 213–219 (2007).
  Article CAS Google Scholar
• Herzenberg, L. A. B-1 cells: the lineage question revisited. Immunol. Rev. 175, 9–22 (2000).
  Article CAS PubMed Google Scholar
• Lalor, P. A., Herzenberg, L. A., Adams, S. & Stall, A. M. Feedback regulation of murine Ly-1 B cell development. Eur. J. Immunol. 19, 507–513 (1989). This study showed that bone marrow cells do not continuously repopulate the peritoneal cavity B-1 cell pool in the steady state.
  Article CAS PubMed Google Scholar
• Deenen, G. J. & Kroese, F. G. Murine peritoneal Ly-1 B cells do not turn over rapidly. Ann. NY Acad. Sci. 651, 70–71 (1992).
  Article CAS PubMed Google Scholar
• Baumgarth, N., Herman, O. C., Jager, G. C., Brown, L. & Herzenberg, L. A. Innate and acquired humoral immunities to influenza virus are mediated by distinct arms of the immune system. Proc. Natl Acad. Sci. USA 96, 2250–2255 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Boes, M. et al. Enhanced B-1 cell development, but impaired IgG antibody responses in mice deficient in secreted IgM. J. Immunol. 160, 4776–4787 (1998).
  CAS PubMed Google Scholar
• Duber, S. et al. Induction of B-cell development in adult mice reveals the ability of bone marrow to produce B-1a cells. Blood 114, 4960–4967 (2009).
  Article CAS PubMed Google Scholar
• Holodick, N. E., Repetny, K., Zhong, X. & Rothstein, T. L. Adult BM generates CD5+ B1 cells containing abundant N-region additions. Eur. J. Immunol. 39, 2383–2394 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Montecino-Rodriguez, E., Leathers, H. & Dorshkind, K. Identification of a B-1 B cell-specified progenitor. Nature Immunol. 7, 293–301 (2006). This study identified the elusive precursor of B-1 cells in the bone marrow of adult mice.
  Article CAS Google Scholar
• Tornberg, U. C. & Holmberg, D. B-1a, B-1b and B-2 B cells display unique VHDJH repertoires formed at different stages of ontogeny and under different selection pressures. EMBO J. 14, 1680–1689 (1995).
  Article CAS PubMed PubMed Central Google Scholar
• Kantor, A. B., Merrill, C. E., Herzenberg, L. A. & Hillson, J. L. An unbiased analysis of VH–D–JH sequences from B-1a, B-1b, and conventional B cells. J. Immunol. 158, 1175–1186 (1997).
  CAS PubMed Google Scholar
• Gregoire, K. E., Goldschneider, I., Barton, R. W. & Bollum, F. J. Ontogeny of terminal deoxynucleotidyl transferase-positive cells in lymphohemopoietic tissues of rat and mouse. J. Immunol. 123, 1347–1352 (1979).
  CAS PubMed Google Scholar
• Gu, H., Forster, I. & Rajewsky, K. Sequence homologies, N sequence insertion and JH gene utilization in VHDJH joining: implications for the joining mechanism and the ontogenetic timing of Ly1 B cell and B-CLL progenitor generation. EMBO J. 9, 2133–2140 (1990).
  Article CAS PubMed PubMed Central Google Scholar
• Chou, M. Y. et al. Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans. J. Clin. Invest. 119, 1335–1349 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Kulik, L. et al. Pathogenic natural antibodies recognizing annexin IV are required to develop intestinal ischemia-reperfusion injury. J. Immunol. 182, 5363–5373 (2009).
  Article CAS PubMed Google Scholar
• Racine, R. & Winslow, G. M. IgM in microbial infections: taken for granted? Immunol. Lett. 125, 79–85 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Hogquist, K. A., Starr, T. K. & Jameson, S. C. Receptor sensitivity: when T cells lose their sense of self. Curr. Biol. 13, R239–R241 (2003).
  Article CAS PubMed Google Scholar
• Hayakawa, K. et al. Positive selection of natural autoreactive B cells. Science 285, 113–116 (1999). This study provided evidence that B-1 cell development is driven by positive selection on self antigens.
  Article CAS PubMed Google Scholar
• Lam, K. P. & Rajewsky, K. B cell antigen receptor specificity and surface density together determine B-1 versus B-2 cell development. J. Exp. Med. 190, 471–477 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Casola, S. et al. B cell receptor signal strength determines B cell fate. Nature Immunol. 5, 317–327 (2004).
  Article CAS Google Scholar
• Esplin, B. L., Welner, R. S., Zhang, Q., Borghesi, L. A. & Kincade, P. W. A differentiation pathway for B1 cells in adult bone marrow. Proc. Natl Acad. Sci. USA 106, 5773–5778 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Solvason, N. et al. Cyclin D2 is essential for BCR-mediated proliferation and CD5 B cell development. Int. Immunol. 12, 631–638 (2000).
  Article CAS PubMed Google Scholar
• Vink, A., Warnier, G., Brombacher, F. & Renauld, J. C. Interleukin 9-induced in vivo expansion of the B-1 lymphocyte population. J. Exp. Med. 189, 1413–1423 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Moon, B. G., Takaki, S., Miyake, K. & Takatsu, K. The role of IL-5 for mature B-1 cells in homeostatic proliferation, cell survival, and Ig production. J. Immunol. 172, 6020–6029 (2004).
  Article CAS PubMed Google Scholar
• Moro, K. et al. Innate production of TH2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphoid cells. Nature 463, 540–544 (2010).
  Article CAS PubMed Google Scholar
• Ansel, K. M., Harris, R. B. & Cyster, J. G. CXCL13 is required for B1 cell homing, natural antibody production, and body cavity immunity. Immunity 16, 67–76 (2002).
  Article CAS PubMed Google Scholar
• Wardemann, H., Boehm, T., Dear, N. & Carsetti, R. B-1a B cells that link the innate and adaptive immune responses are lacking in the absence of the spleen. J. Exp. Med. 195, 771–780 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Rothaeusler, K. & Baumgarth, N. Evaluation of intranuclear BrdU detection procedures for use in multicolor flow cytometry. Cytometry A 69, 249–259 (2006).
  Article PubMed PubMed Central Google Scholar
• Kretschmer, K., Stopkowicz, J., Scheffer, S., Greten, T. F. & Weiss, S. Maintenance of peritoneal B-1a lymphocytes in the absence of the spleen. J. Immunol. 173, 197–204 (2004).
  Article CAS PubMed Google Scholar
• McIntyre, T. M., Holmes, K. L., Steinberg, A. D. & Kastner, D. L. CD5+ peritoneal B cells express high levels of membrane, but not secretory, C mu mRNA. J. Immunol. 146, 3639–3645 (1991).
  CAS PubMed Google Scholar
• Tumang, J. R., Frances, R., Yeo, S. G. & Rothstein, T. L. Spontaneously Ig-secreting B-1 cells violate the accepted paradigm for expression of differentiation-associated transcription factors. J. Immunol. 174, 3173–3177 (2005).
  Article CAS PubMed Google Scholar
• Fairfax, K. A. et al. Different kinetics of Blimp-1 induction in B cell subsets revealed by reporter gene. J. Immunol. 178, 4104–4111 (2007).
  Article CAS PubMed Google Scholar
• Savitsky, D. & Calame, K. B-1 B lymphocytes require Blimp-1 for immunoglobulin secretion. J. Exp. Med. 203, 2305–2314 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Choi, Y. S. & Baumgarth, N. Dual role for B-1a cells in immunity to influenza virus infection. J. Exp. Med. 205, 3053–3064 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Baumgarth, N. et al. B-1 and B-2 cell-derived immunoglobulin M antibodies are nonredundant components of the protective response to influenza virus infection. J. Exp. Med. 192, 271–280 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Boes, M., Prodeus, A. P., Schmidt, T., Carroll, M. C. & Chen, J. A critical role of natural immunoglobulin M in immediate defense against systemic bacterial infection. J. Exp. Med. 188, 2381–2386 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Haas, K. M., Poe, J. C., Steeber, D. A. & Tedder, T. F. B-1a and B-1b cells exhibit distinct developmental requirements and have unique functional roles in innate and adaptive immunity to S. pneumoniae. Immunity 23, 7–18 (2005).
  Article CAS PubMed Google Scholar
• Jayasekera, J. P., Moseman, E. A. & Carroll, M. C. Natural antibody and complement mediate neutralization of influenza virus in the absence of prior immunity. J. Virol. 81, 3487–3494 (2007).
  Article CAS PubMed PubMed Central 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
• Zhou, Z. H. et al. The broad antibacterial activity of the natural antibody repertoire is due to polyreactive antibodies. Cell Host Microbe 1, 51–61 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Baumgarth, N. A two-phase model of B-cell activation. Immunol. Rev. 176, 171–180 (2000).
  Article CAS PubMed Google Scholar
• Suzuki, K., Maruya, M., Kawamoto, S. & Fagarasan, S. Roles of B-1 and B-2 cells in innate and acquired IgA-mediated immunity. Immunol. Rev. 237, 180–190 (2010).
  Article CAS PubMed 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
• Tarlinton, D. M., McLean, M. & Nossal, G. J. B1 and B2 cells differ in their potential to switch immunoglobulin isotype. Eur. J. Immunol. 25, 3388–3393 (1995).
  Article CAS PubMed Google Scholar
• Thurnheer, M. C., Zuercher, A. W., Cebra, J. J. & Bos, N. A. B1 cells contribute to serum IgM, but not to intestinal IgA, production in gnotobiotic Ig allotype chimeric mice. J. Immunol. 170, 4564–4571 (2003).
  Article CAS PubMed Google Scholar
• Kroese, F. G. et al. Many of the IgA producing plasma cells in murine gut are derived from self-replenishing precursors in the peritoneal cavity. Int. Immunol. 1, 75–84 (1989). This seminal study links IgA production in the gut to B-1 cells and therefore links B-1 cells to the regulation of gut homeostasis and mucosal immunity.
  Article CAS PubMed Google Scholar
• Kroese, F. G., de Waard, R. & Bos, N. A. B-1 cells and their reactivity with the murine intestinal microflora. Semin. Immunol. 8, 11–18 (1996).
  Article CAS PubMed Google Scholar
• Macpherson, A. J. & Slack, E. The functional interactions of commensal bacteria with intestinal secretory IgA. Curr. Opin. Gastroenterol. 23, 673–678 (2007).
  Article CAS PubMed Google Scholar
• De-Gennaro, L. A., Popi, A. F., Almeida, S. R., Lopes, J. D. & Mariano, M. B-1 cells modulate oral tolerance in mice. Immunol. Lett. 124, 63–69 (2009).
  Article CAS PubMed Google Scholar
• Boes, M. et al. Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM. Proc. Natl Acad. Sci. USA 97, 1184–1189 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Shaw, P. X. et al. Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity. J. Clin. Invest. 105, 1731–1740 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Chen, Y., Park, Y. B., Patel, E. & Silverman, G. J. IgM antibodies to apoptosis-associated determinants recruit C1q and enhance dendritic cell phagocytosis of apoptotic cells. J. Immunol. 182, 6031–6043 (2009).
  Article CAS PubMed Google Scholar
• Taylor, P. R. et al. Macrophage receptors and immune recognition. Annu. Rev. Immunol. 23, 901–944 (2005).
  Article CAS PubMed Google Scholar
• Rodriguez-Manzanet, R. et al. T and B cell hyperactivity and autoimmunity associated with niche-specific defects in apoptotic body clearance in TIM-4-deficient mice. Proc. Natl Acad. Sci. USA 107, 8706–8711 (2010). These authors identified TIM4 as a scavenger receptor expressed by macrophages and B-1 cells and described an antibody-independent mechanism by which B-1 cells can function as regulators of tissue homeostasis.
  Article CAS PubMed PubMed Central Google Scholar
• O'Garra, A. et al. Ly-1 B (B-1) cells are the main source of B cell-derived interleukin-10. Eur. J. Immunol. 22, 711–717 (1992).
  Article CAS PubMed Google Scholar
• Lampropoulou, V. et al. Suppressive functions of activated B cells in autoimmune diseases reveal the dual roles of Toll-like receptors in immunity. Immunol. Rev. 233, 146–161 (2010).
  Article CAS PubMed Google Scholar
• Ha, S. A. et al. Regulation of B1 cell migration by signals through Toll-like receptors. J. Exp. Med. 203, 2541–2550 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Murakami, M. et al. Oral administration of lipopolysaccharides activates B-1 cells in the peritoneal cavity and lamina propria of the gut and induces autoimmune symptoms in an autoantibody transgenic mouse. J. Exp. Med. 180, 111–121 (1994).
  Article CAS PubMed Google Scholar
• Nisitani, S., Tsubata, T., Murakami, M. & Honjo, T. Administration of interleukin-5 or -10 activates peritoneal B-1 cells and induces autoimmune hemolytic anemia in anti-erythrocyte autoantibody-transgenic mice. Eur. J. Immunol. 25, 3047–3052 (1995).
  Article CAS PubMed Google Scholar
• Yang, Y., Tung, J. W., Ghosn, E. E. & Herzenberg, L. A. Division and differentiation of natural antibody-producing cells in mouse spleen. Proc. Natl Acad. Sci. USA 104, 4542–4546 (2007).
  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
• Chumley, M. J., Dal Porto, J. M. & Cambier, J. C. The unique antigen receptor signaling phenotype of B-1 cells is influenced by locale but induced by antigen. J. Immunol. 169, 1735–1743 (2002).
  Article CAS PubMed Google Scholar
• Morris, D. L. & Rothstein, T. L. Abnormal transcription factor induction through the surface immunoglobulin M receptor of B-1 lymphocytes. J. Exp. Med. 177, 857–861 (1993). This study demonstrates the unique differentiation stage of peritoneal B-1 cells, showing that these cells are unable to enter the cell cycle after BCR crosslinking but that BCR stimulation does not affect the survival of B-1 cells.
  Article CAS PubMed Google Scholar
• Bikah, G., Carey, J., Ciallella, J. R., Tarakhovsky, A. & Bondada, S. CD5-mediated negative regulation of antigen receptor-induced growth signals in B-1 B cells. Science 274, 1906–1909 (1996).
  Article CAS PubMed Google Scholar
• Ochi, H. & Watanabe, T. Negative regulation of B cell receptor-mediated signaling in B-1 cells through CD5 and Ly49 co-receptors via Lyn kinase activity. Int. Immunol. 12, 1417–1423 (2000).
  Article CAS PubMed Google Scholar
• Holodick, N. E., Tumang, J. R. & Rothstein, T. L. Continual signaling is responsible for constitutive ERK phosphorylation in B-1a cells. Mol. Immunol. 46, 3029–3036 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Sen, G. et al. Defective CD19-dependent signaling in B-1a and B-1b B lymphocyte subpopulations. Mol. Immunol. 39, 57–68 (2002).
  Article CAS PubMed Google Scholar
• Dal Porto, J. M., Burke, K. & Cambier, J. C. Regulation of BCR signal transduction in B-1 cells requires the expression of the Src family kinase Lck. Immunity 21, 443–453 (2004).
  Article PubMed Google Scholar
• Ulivieri, C., Valensin, S., Majolini, M. B., Matthews, R. J. & Baldari, C. T. Normal B-1 cell development but defective BCR signaling in Lck −/− mice. Eur. J. Immunol. 33, 441–445 (2003).
  Article CAS PubMed Google Scholar
• Frances, R., Tumang, J. R. & Rothstein, T. L. B-1 cells are deficient in Lck: defective B cell receptor signal transduction in B-1 cells occurs in the absence of elevated Lck expression. J. Immunol. 175, 27–31 (2005).
  Article CAS PubMed Google Scholar
• Hoffmann, A. et al. Siglec-G is a B1 cell-inhibitory receptor that controls expansion and calcium signaling of the B1 cell population. Nature Immunol. 8, 695–704 (2007).
  Article CAS Google Scholar
• Wong, S. C. et al. Peritoneal CD5+ B-1 cells have signaling properties similar to tolerant B cells. J. Biol. Chem. 277, 30707–30715 (2002).
  Article CAS PubMed Google Scholar
• Hippen, K. L., Tze, L. E. & Behrens, T. W. CD5 maintains tolerance in anergic B cells. J. Exp. Med. 191, 883–890 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Bell, S. E. & Goodnow, C. C. A selective defect in IgM antigen receptor synthesis and transport causes loss of cell surface IgM expression on tolerant B lymphocytes. EMBO J. 13, 816–826 (1994).
  Article CAS PubMed PubMed Central Google Scholar
• Blery, M., Tze, L., Miosge, L. A., Jun, J. E. & Goodnow, C. C. Essential role of membrane cholesterol in accelerated BCR internalization and uncoupling from NF-κB in B cell clonal anergy. J. Exp. Med. 203, 1773–1783 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Fulcher, D. A. & Basten, A. Reduced life span of anergic self-reactive B cells in a double-transgenic model. J. Exp. Med. 179, 125–134 (1994).
  Article CAS PubMed Google Scholar
• Durand, C. A. et al. Phosphoinositide 3-kinase p110δ regulates natural antibody production, marginal zone and B-1 B cell function, and autoantibody responses. J. Immunol. 183, 5673–5684 (2009).
  Article CAS PubMed Google Scholar
• Cole, L. E. et al. Antigen-specific B-1a antibodies induced by Francisella tularensis LPS provide long-term protection against F. tularensis LVS challenge. Proc. Natl Acad. Sci. USA 106, 4343–4348 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Alugupalli, K. R. et al. B1b lymphocytes confer T cell-independent long-lasting immunity. Immunity 21, 379–390 (2004). This study provides evidence for the existence of B-1b cell-derived memory responses.
  Article CAS PubMed Google Scholar
• Ohdan, H. et al. Mac-1-negative B-1b phenotype of natural antibody-producing cells, including those responding to Galα1,3Gal epitopes in α1,3-galactosyltransferase-deficient mice. J. Immunol. 165, 5518–5529 (2000).
  Article CAS PubMed Google Scholar
• Askenase, P. W., Szczepanik, M., Itakura, A., Kiener, C. & Campos, R. A. Extravascular T-cell recruitment requires initiation begun by Vα14+ NKT cells and B-1 B cells. Trends Immunol. 25, 441–449 (2004). This review summarizes several studies that showed that the early production of IgM by B-1 cells and interaction of B-1 cells with NKT cells are required for the initiation of DTH responses.
  Article CAS PubMed Google Scholar
• Kerfoot, S. M., Szczepanik, M., Tung, J. W. & Askenase, P. W. Identification of initiator B cells, a novel subset of activation-induced deaminase-dependent B-1-like cells that mediate initiation of contact sensitivity. J. Immunol. 181, 1717–1727 (2008).
  Article CAS PubMed Google Scholar
• Takahashi, T. & Strober, S. Natural killer T cells and innate immune B cells from lupus-prone NZB/W mice interact to generate IgM and IgG autoantibodies. Eur. J. Immunol. 38, 156–165 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Watanabe, N. et al. Migration and differentiation of autoreactive B-1 cells induced by activated γδ T cells in antierythrocyte immunoglobulin transgenic mice. J. Exp. Med. 192, 1577–1586 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Zhang, M. et al. Identification of the target self-antigens in reperfusion injury. J. Exp. Med. 203, 141–152 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Gil-Cruz, C. et al. The porin OmpD from nontyphoidal Salmonella is a key target for a protective B1b cell antibody response. Proc. Natl Acad. Sci. USA 106, 9803–9808 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Alam, C., Valkonen, S., Ohls, S., Tornqvist, K. & Hanninen, A. Enhanced trafficking to the pancreatic lymph nodes and auto-antigen presentation capacity distinguishes peritoneal B lymphocytes in non-obese diabetic mice. Diabetologia 53, 346–355 (2010).
  Article CAS PubMed Google Scholar
• Riggs, J. E. et al. Mls presentation by peritoneal cavity B cells. Immunobiology 209, 255–264 (2004).
  Article CAS PubMed Google Scholar
• Ryan, G. A. et al. B1 cells promote pancreas infiltration by autoreactive T cells. J. Immunol. 185, 2800–2807 (2010).
  Article CAS PubMed Google Scholar
• Sun, C. M., Deriaud, E., Leclerc, C. & Lo-Man, R. Upon TLR9 signaling, CD5+ B cells control the IL-12-dependent Th1-priming capacity of neonatal DCs. Immunity 22, 467–477 (2005).
  CAS PubMed Google Scholar
• Casali, P., Burastero, S. E., Nakamura, M., Inghirami, G. & Notkins, A. L. Human lymphocytes making rheumatoid factor and antibody to ssDNA belong to Leu-1+ B-cell subset. Science 236, 77–81 (1987).
  Article CAS PubMed Google Scholar
• Hardy, R. R., Hayakawa, K., Shimizu, M., Yamasaki, K. & Kishimoto, T. Rheumatoid factor secretion from human Leu-1+ B cells. Science 236, 81–83 (1987). References 117 and 118 described the presence of CD5+ B cells that generate self-reactive antibodies in humans.
  Article CAS PubMed Google Scholar
• Kasaian, M. T. & Casali, P. Autoimmunity-prone B-1 (CD5 B) cells, natural antibodies and self recognition. Autoimmunity 15, 315–329 (1993).
  Article CAS PubMed Google Scholar
• Kasaian, M. T., Ikematsu, H. & Casali, P. Identification and analysis of a novel human surface CD5− B lymphocyte subset producing natural antibodies. J. Immunol. 148, 2690–2702 (1992).
  CAS PubMed Google Scholar
• Boursier, L., Montalto, S. A., Raju, S., Culora, G. & Spencer, J. Characterization of cells of the B lineage in the human adult greater omentum. Immunology 119, 90–97 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Yuling, H. et al. CD19+CD5+ B cells in primary IgA nephropathy. J. Am. Soc. Nephrol. 19, 2130–2139 (2008).
  Article PubMed PubMed Central Google Scholar
• Blair, P. A. et al. CD19+CD24hiCD38hi B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic lupus erythematosus patients. Immunity 32, 129–140 (2010).
  Article CAS PubMed Google Scholar
• Carsetti, R., Rosado, M. M. & Wardmann, H. Peripheral development of B cells in mouse and man. Immunol. Rev. 197, 179–191 (2004).
  Article PubMed Google Scholar
• Dorner, T., Foster, S. J., Farner, N. L. & Lipsky, P. E. Somatic hypermutation of human immunoglobulin heavy chain genes: targeting of RGYW motifs on both DNA strands. Eur. J. Immunol. 28, 3384–3396 (1998).
  Article CAS PubMed Google Scholar
• Lee, J., Kuchen, S., Fischer, R., Chang, S. & Lipsky, P. E. Identification and characterization of a human CD5+ pre-naive B cell population. J. Immunol. 182, 4116–4126 (2009).
  Article CAS PubMed Google Scholar
• Pillai, S., Cariappa, A. & Moran, S. T. Marginal zone B cells. Annu. Rev. Immunol. 23, 161–196 (2005).
  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).
  Article CAS PubMed Google Scholar
• Carsetti, R., Pantosti, A. & Quinti, I. Impairment of the antipolysaccharide response in splenectomized patients is due to the lack of immunoglobulin M memory B cells. J. Infect. Dis. 193, 1189–1190 (2006).
  Article PubMed 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).
  Article CAS PubMed PubMed Central 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
• Wardemann, H. et al. Predominant autoantibody production by early human B cell precursors. Science 301, 1374–1377 (2003).
  Article CAS PubMed Google Scholar
• Rakhmanov, M. et al. Circulating CD21low B cells in common variable immunodeficiency resemble tissue homing, innate-like B cells. Proc. Natl Acad. Sci. USA 106, 13451–13456 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Ehrhardt, G. R. et al. Expression of the immunoregulatory molecule FcRH4 defines a distinctive tissue-based population of memory B cells. J. Exp. Med. 202, 783–791 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Moir, S. et al. Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals. J. Exp. Med. 205, 1797–1805 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Baumgarth, N. B-cell immunophenotyping. Methods Cell Biol. 75, 643–662 (2004).
  Article PubMed Google Scholar
• Baumgarth, N. & Roederer, M. A practical approach to multicolor flow cytometry for immunophenotyping. J. Immunol. Methods 243, 77–97 (2000).
  Article CAS PubMed Google Scholar
• Ghosn, E. E., Yang, Y., Tung, J. & Herzenberg, L. A. CD11b expression distinguishes sequential stages of peritoneal B-1 development. Proc. Natl Acad. Sci. USA 105, 5195–5200 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Hastings, W. D., Gurdak, S. M., Tumang, J. R. & Rothstein, T. L. CD5+/Mac-1− peritoneal B cells: a novel B cell subset that exhibits characteristics of B-1 cells. Immunol. Lett. 105, 90–96 (2006).
  Article CAS PubMed Google Scholar
• Wells, S. M., Kantor, A. B. & Stall, A. M. CD43 (S7) expression identifies peripheral B cell subsets. J. Immunol. 153, 5503–5515 (1994).
  CAS PubMed Google Scholar
• Cong, Y. Z., Rabin, E. & Wortis, H. H. Treatment of murine CD5− B cells with anti-Ig, but not LPS, induces surface CD5: two B-cell activation pathways. Int. Immunol. 3, 467–476 (1991). This study showed that CD5 expression can be upregulated on B-2 cells in response to BCR-mediated signalling and forms the basis of the 'induced differentiation hypothesis' of B-1 cell development.
  Article CAS PubMed Google Scholar
• Emslie, D. et al. Oct2 enhances antibody-secreting cell differentiation through regulation of IL-5 receptor α chain expression on activated B cells. J. Exp. Med. 205, 409–421 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Won, W. J. & Kearney, J. F. CD9 is a unique marker for marginal zone B cells, B1 cells, and plasma cells in mice. J. Immunol. 168, 5605–5611 (2002).
  Article CAS PubMed Google Scholar
• Martin, F. & Kearney, J. F. Marginal-zone B cells. Nature Rev. Immunol. 2, 323–335 (2002).
  Article CAS Google Scholar
• Kantor, A. B. & Herzenberg, L. A. Origin of murine B cell lineages. Annu. Rev. Immunol. 11, 501–538 (1993).
  Article CAS PubMed Google Scholar
• Bouaziz, J. D., Yanaba, K. & Tedder, T. F. Regulatory B cells as inhibitors of immune responses and inflammation. Immunol. Rev. 224, 201–214 (2008).
  Article CAS PubMed Google Scholar
• Yanaba, K., Bouaziz, J. D., Matsushita, T., Tsubata, T. & Tedder, T. F. The development and function of regulatory B cells expressing IL-10 (B10 cells) requires antigen receptor diversity and TLR signals. J. Immunol. 182, 7459–7472 (2009).
  Article CAS PubMed Google Scholar
• Hao, Z. & Rajewsky, K. Homeostasis of peripheral B cells in the absence of B cell influx from the bone marrow. J. Exp. Med. 194, 1151–1164 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Kawahara, T., Ohdan, H., Zhao, G., Yang, Y. G. & Sykes, M. Peritoneal cavity B cells are precursors of splenic IgM natural antibody-producing cells. J. Immunol. 171, 5406–5414 (2003).
  Article CAS PubMed Google Scholar
• Rosado, M. M. et al. From the fetal liver to spleen and gut: the highway to natural antibody. Mucosal Immunol. 2, 351–361 (2009).
  Article CAS PubMed Google Scholar
• Kurosaki, T., Aiba, Y., Kometani, K., Moriyama, S. & Takahashi, Y. Unique properties of memory B cells of different isotypes. Immunol. Rev. 237, 104–116 (2010).
  Article CAS PubMed Google Scholar