Antigen presentation by splenic B cells: resting B cells are ineffective, whereas activated B cells are effective accessory cells for T cell responses (original) (raw)
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Tolerogenicity of resting and activated B cells
Journal of Experimental Medicine, 1994
Antigen presentation by resting splenic B cells has been shown previously to induce T helper 1 cell (Th1) anergy. In contrast to expectations, it was found here that B cells treated with F(ab')2 goat anti-mouse immunoglobulin (IgM) for 24 or 48 h also presented antigen (Ag) to Th1 cells in a manner that induced dramatic Ag-specific proliferative inactivation. The tolerogenicity of the anti-Ig-treated B cells was consistent with the observation that these B cells were only slightly more efficient than resting B cells in stimulating human gamma globulin (HGG)-induced proliferation of HGG-specific Th1 cells in primary cultures. The activated B cells were, however, more efficient than resting B cells in stimulating a primary mixed leukocyte reaction, and exhibited increased expression of major histocompatibility complex class II molecules, RL388 Ag and transferrin receptor. In addition, unlike resting B cells, which expressed little detectable B7, anti-Ig-treated B cells expressed h...
Only a small proportion of splenic B cells in adults are short-lived virgin cells
European Journal of Immunology, 1993
A cohort of newly produced virgin B cells was followed from the marrow to the spleen of non-immunized clean rats, which showed minimal antigen-driven proliferation of B cells in their spleens. The progenitors of this cohort of virgin cells were labeled in vivo over 12 h with the thymidine analogue 5-bromo-2′-deoxyuridine (BrdUrd) and their non proliferating progeny left the marrow 2-3 days later. This coincided with the arrival of labeled B cells in the red pulp and T zones of the spleen. These appear to be short-lived as few remained a week after the label was given. The short-lived newly produced virgin B cells can only comprise a minority of splenic B cells, for it is shown that only 20% of splenic B cells are found in the red pulp and T zone. It is calculated that newly produced virgin B cells are likely to make up between 5% and 10% of splenic B cells. In the marginal zones and follicular mantle respective medians of 3.3% and 1.8% were already labeled at 1 day from the start of the BrdUrd pulse. The appearance of these cells seems likely to result from antigen-driven B cell proliferation outside the marrow, for labeled virgin B cells have not started to leave the marrow at this stage. During day 2 and 3 the proportion of labeled follicular mantle B cells rose to 3.4%, which might in part reflect the recruitment of newly produced virgin B cells to the pool of recirculating follicular B cells. After day 3 in the follicles and day 1 in the marginal zones the proportion of labeled cells did not vary significantly through day 7. This appears to confirm the comparative longevity of the cells in these zones, which contain 80% of the non-proliferating splenic B cells of adult rats.
transplantation. However, the impact of T-cell depletion by antibodies on B-cell homeostasis is poorly understood. Using a mouse model of allosensitization with skin allograft, we investigated whether targeting T cells by anti-CD3e alters peripheral B-cell homeostasis and alloantibody responses following B-cell depletion by anti-CD20. We found that anti-CD3e induced a discrete B220 lo , but not a conventional B220 hi subset, in the spleens of the allosensitized mice 14 days after anti-CD20 treatment. The splenic B220 lo cells were refractory to anti-CD20 depletion. Flow cytometry revealed that the splenic B220 lo cells were phenotypically similar to the B220 lo AA4.1 1 CD23 2 sIgM lo sIgD 2 developing B cells (pre-B to immature B) normally presented in the bone marrow. Despite the presence of the splenic B220 lo cells, mice treated with combined anti-CD3e/CD20 produced limited alloantibodies in response to the primary skin allografts. Alloantibody production increased significantly in the mice following re-immunization by donor-specific splenocytes. We conclude that anti-CD3e can induce an expansion of B220 lo B cells in the spleens after B-cell depletion by anti-CD20. These B cells are not producing alloantibodies, but re-immunization of the mice with alloantigen leads to risk of alloantibody response. Fig. 5. Splenic B220 lo cells have the potential being primed to produce alloantibodies. (A) Flow cytometric antibody binding experiments
Evidence for selection of a population of multi-reactive B cells into the splenic marginal zone
International Immunology, 1997
Antibody reactivity to self-antigens is a normal component of the immune system. To study the mechanism by which self-reactive B cells are generated and maintained, we analyzed B cell development in transgenic mice that express a rearranged V H 81X heavy chain from the preimmune repertoire. In these mice, Ͼ95% of B cells express the transgene in association with a variety of kappa light chains but V κ 1C being the dominant light chain. These transgenic B cells with identical V κ 1C-J κ 5 joins do not normally secrete IgM in vivo, but antibodies derived from these B
Characterization of splenic CD21 hi T2 B cells
Immunol Res, 2007
B cell development is a highly regulated process that initiates in the bone marrow (BM) of adult mice. After reaching the IgM + immature stage in the BM, these B cells migrate to the spleen to complete maturation and incorporation into the long-lived peripheral lymphocyte pool. Studies have identified these splenic immature B cells, and have further attempted to delineate the sequence whereby they transition into mature B cells. As such, these immature splenic populations are termed transitional B cells and have been the focus of intense study. The review summarizes the phenotype and currently known functions of the four putative transitional B cell subsets identified to date. Although most appear to represent short-lived transitional B cells, the CD21 hi T2 B cell population exhibits a number of qualities that question its label as a transitional B cell subset.
The Journal of Immunology, 2012
In the adult spleen, CD19 + CD45R 2/lo (19 + 45R lo ) lymphocytes of embryonic origin exist as a distinct population to that of the conventional B cell lineage. These cells display a plasmablast phenotype, and they spontaneously secrete IgG1 and IgA, whereas the bone marrow population of 19 + 45R lo cells contains B1 progenitors. In this study, we show that 19 + 45R lo cells are also present in Peyer's patches and in the spleen throughout the life span of wild-type mice, beginning at postnatal day 7. Although this population is heterogeneous, the surface phenotype of most of these cells distinguishes them from follicular, transitional, marginal zone, and B1 cells. In CBA/CaHN mice, few 19 + 45R lo cells were detected at postnatal day 7, and none was observed in the adult spleen. Splenic 19 + 45R lo cells exhibited homeostatic BrdU uptake in vivo and actively transcribed cell cycle genes. When transferred to immunodeficient RAG2 2/2 gchain 2/2 recipient mice, 19 + 45R lo cells survived and differentiated into IgG1-and IgAplasma cells. Moreover, in vitro stimulation of splenic 19 + 45R lo cells with LPS, CpG, BAFF/IL4, and CD40/IL4 induced cell proliferation, IgG1/IgA secretion and the release of IL-10, suggesting a potential immunoregulatory role for this subset of innatelike B cells.
International Immunology, 2000
This study attempted to evaluate and compare the role of various B cell-specific markers for antiviral immune responses in mouse strains lacking molecules belonging to the B cell receptor (BCR) complex (IgM, Igα and C κ), the co-stimulatory molecules (CD19 and CD22), the protein kinases [Bruton's tyrosine kinase (Btk)] or the transcription factors (OBF-1). These mice were tested in two model infections [vesicular stomatitis virus (VSV) and lymphocytic choriomeningitis virus (LCMV)] using T cell-independent (TI) or T cell-dependent (TD) antigens. All mice controlled an LCMV infection indicating that cytotoxic T cell functions were within normal ranges. In contrast, OBF-1-/mice were partially protected and mb-1 ∆c/∆c mice not at all protected against VSV infection, a virus that is controlled virtually exclusively by neutralizing antibodies. Susceptibility to VSV infection was correlated with structural defects in the spleen: absence of mature B cells and follicles with marginal zone macrophages and absence of germinal centers with follicular dendritic cells correlated with lack or substantial reduction of protective IgM and IgG responses respectively. The lack of κ light chain did not affect the neutralizing response, indicating that it could easily be replaced by the λ chain. Absence of the co-stimulatory molecules CD19 and CD22 or of the signaling molecule Btk had modulating effects, but did not increase susceptibility to VSV or LCMV. Our findings suggest that there are crucial molecules for B cell activation at the beginning (BCR complex) and the end (transcription) of the signaling cascade, whereas fine-tuning factors modulating the response in between exhibit considerable functional overlap.
Journal of Experimental Medicine, 2002
Splenectomized individuals are prone to overwhelming infections with encapsulated bacteria and splenectomy of mice increases susceptibility to streptococcal infections, yet the exact mechanism by which the spleen protects against such infections is unknown. Using congenitally asplenic mice as a model, we show that the spleen is essential for the generation of B-1a cells, a B cell population that cooperates with the innate immune system to control early bacterial and viral growth. Splenectomy of wild-type mice further demonstrated that the spleen is also important for the survival of B-1a cells. Transfer experiments demonstrate that lack of these cells, as opposed to the absence of the spleen per se, is associated with an inability to mount a rapid immune response against streptococcal polysaccharides. Thus, absence of the spleen and the associated increased susceptibility to streptococcal infections is correlated with lack of B-1a B cells. These findings reveal a hitherto unknown ro...