B-1a and B-1b Cells Exhibit Distinct Developmental Requirements and Have Unique Functional Roles in Innate and Adaptive Immunity to S. pneumoniae

Haas, Karen M.; Poe, Jonathan C.; Steeber, Douglas A.; Tedder, Thomas F.

doi:10.1016/j.immuni.2005.04.011

Cited by 525 publications

(639 citation statements)

References 31 publications

(4 reference statements)

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“…As a caveat, it should be noted that a subset of regulatory CD5 þ CD1d high IL-10 producing B cells (B1 cells) fails to be depleted by anti-CD20 antibodies. 43 Interestingly, the secretion of autoantibodies is a function exclusive to the B1 subset, and the majority of human cancer patients mount specific autoantibody responses against their tumors. 44 Moreover, the population of CD20-resistant B cells has been reported to enhance A20 lymphoma growth in an IL-10-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines

et al. 2013

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Immunogenic cell death induced by cytotoxic compounds contributes to the success of selected chemotherapies by eliciting a protective anticancer immune response, which is mediated by CD4 þ and CD8 þ T cells producing interferon-c. In many instances, cancer progression is associated with high titers of tumor-specific antibodies, which become detectable in the serum, but whose functional relevance is elusive. Here, we explored the role of humoral immune responses in the anticancer efficacy of anthracyclines. Chemotherapy reduced the number of tumor-infiltrating B cells, and failed to promote humoral responses against immunodominant tumor antigens. Although anthracycline-based anticancer chemotherapies failed in T cell-deficient mice, they successfully reduced the growth of cancers developing in mice lacking B lymphocytes (due to the injection of a B-celldepleting anti-CD20 antibody), immunoglobulins (Igs) or Ig receptors (Fc receptor) due to genetic manipulations. These results suggest that the humoral arm of antitumor immunity is dispensable for the immune-dependent therapeutic effect of anthracyclines against mouse sarcoma. In addition, we show here that the titers of IgA and IgG antibodies directed against an autoantigen appearing at the cell surface of tumor cells post chemotherapy (calreticulin, CRT) did not significantly increase in patients treated with anthracyclines, and that anti-CRT antibodies had no prognostic or predictive significance. Collectively, our data indicate that humoral anticancer immune responses differ from cellular responses in, thus far, that they do not contribute to the success of anthracycline-mediated anticancer therapies in human breast cancers and mouse sarcomas.

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Section: Discussionmentioning

confidence: 99%

Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines

et al. 2013

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“…This indicates that disruption of the TLR signaling pathway primarily impairs innate immune protection mechanisms. The recent work from Tedder and colleagues (6) has revealed that B-1a cells are a crucial component of innate humoral responses. We thus propose that TLR stimulation in the course of natural infection allows a rapid raise of the production of protective natural Abs by B-1 and MZ B cells.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, there is increasing evidence of a broader role for MZ B cells in both T-independent (TI) and T-dependent (TD) immune responses (3,4). It has recently been documented that B-1b cells are mostly responsible for the adaptive immune response to TI Ag and exert a memory function (5,6). Both B-1a and MZ B cells express polyreactive specificities with low affinities to a broad range of Ags and are thus responsible for the production of natural Abs, thereby contributing to innate immunity (1,6).…”

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confidence: 99%

“…It has recently been documented that B-1b cells are mostly responsible for the adaptive immune response to TI Ag and exert a memory function (5,6). Both B-1a and MZ B cells express polyreactive specificities with low affinities to a broad range of Ags and are thus responsible for the production of natural Abs, thereby contributing to innate immunity (1,6). Conversely, FO B are primarily recruited by TD Ags.…”

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confidence: 99%

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TLR Agonists Selectively Promote Terminal Plasma Cell Differentiation of B Cell Subsets Specialized in Thymus-Independent Responses

Genestier¹,

Taillardet

Mondière

et al. 2007

The Journal of Immunology

258

270

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Naive murine B cells are known to proliferate and differentiate in response to LPS or CpG, which bind to TLR4 and TLR9, respectively. However, the naive murine B cell compartment is heterogeneous and comprises four different B cell subsets: B-1a, B-1b, marginal zone (MZ), and follicular (FO) B cells. B-1a, B-1b, and MZ B cells are specialized in the response to thymus-independent Ag, and FO B cells are involved in the response to thymus-dependent Ag. This study was undertaken to compare those four naive B cell subsets for their responses to TLR agonists. Quantitative RT-PCR analysis revealed that expression of TLR transcripts differs quantitatively but not qualitatively from one subset to the other. All TLR agonists, with the exception of flagellin and poly(I:C), stimulate B cell proliferation whatever the subset considered. However, TLR ligation leads to massive differentiation of B-1 and MZ B cells into mature plasma cells (PC) but only marginally promotes PC differentiation of FO B cells. Moreover, TLR stimulation strongly up-regulates expression of Blimp-1 and XBP-1S, two transcription factors known to be instrumental in PC differentiation, in B-1 and MZ B cells but not in FO B cells. Altogether, our findings suggest that B-1 and MZ B cells are poised to PC differentiation in response to the microbial environment and that TLR agonists can be instrumental in stimulating Ab-mediated innate immune protection during microbial infections.

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“…B1 B cells are the major source of natural immunoglobulin in normal unimmunized mice, providing a vital front line defense against bacterial and viral infection [4][5][6][7][8]. This function is associated with a skewed repertoire containing autoreactive specificities, one manifestation of which is expression of phosphatidylcholine (PtC)-binding V H 11 and V H 12 by a substantial portion of peritoneal B1 cells in unimmunized mice [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

PD‐L2 expression extends beyond dendritic cells/macrophages to B1 cells enriched for V_H11/V_H12 and phosphatidylcholine binding

et al. 2007

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B1 B cells are the major source of natural antibody that is essential for innate immunity. The B1 repertoire is skewed toward production of phosphatidylcholine (PtC)-binding V H 11 and V H 12 immunoglobulin that plays a key role in immune defense against bacterial infection. Programmed death-ligand 2 (PD-L2) is a ligand for the immunosuppressive receptor programmed death-1 (PD-1). It has been reported that expression of PD-L2 is restricted to dendritic cells and macrophages in mice. Here we show that 50-70% of resting peritoneal B1 cells express PD-L2, which is not present or inducible on conventional B2 B cells or PD-L2 -B1 cells. Although PD-L2 + and PD-L2 -B1 cells are similar in proliferative responses and spontaneous immunoglobulin secretion, PD-L2 + B1 cells are highly enriched for expression of V H 11 and V H 12 genes and encompass the bulk of PtC-binding B1 cells. These findings extend the range of known PD-L2 expression to B cells and show that B1 cells identified by this marker express a specific repertoire associated with anti-bacterial immunity. IntroductionB1 B cells comprise a unique subset of B cells distinguished phenotypically, ontogenetically, and functionally from conventional (B2) B cells [1][2][3]. B1 B cells are the major source of natural immunoglobulin in normal unimmunized mice, providing a vital front line defense against bacterial and viral infection [4][5][6][7][8]. This function is associated with a skewed repertoire containing autoreactive specificities, one manifestation of which is expression of phosphatidylcholine (PtC)-binding V H 11 and V H 12 by a substantial portion of peritoneal B1 cells in unimmunized mice [9][10][11]. PtC is the polar headgroup of common membrane phospholipids. Reconstitution of anti-PtC IgM in sIgM-deficient mice substantially reduced the bacterial load in a cecal ligation and puncture model [5]. Thus, V H 11/V H 12-expressing B1 cells play an important role in immunity; considering that PtC-binding B1 cells recognize protease-treated autologous erythrocytes, they may play a role in hemolytic autoimmune dyscrasias as well [10,12].B cells, like T cells, express programmed death-1 (PD-1), engagement of which negatively regulates B cell activity in vitro [13]. Surface levels of PD-1 are upregulated by BCR stimulation and down-regulated by Results and discussionPeritoneal B1 cells uniquely express PD-L2To evaluate PD-L1 and PD-L2 expression, cells from normal peritoneal washout fluids and spleens were stained with fluorescent antibodies to identify B1 cells, B2 cells and T cells and were counterstained to detect PD-L1 and PD-L2. Like B2 cells and T cells, B1 cells expressed a basal level of PD-L1, although to a much greater extent (Fig. 1A). Surprisingly, we found that a significant portion of peritoneal B1 cells (50-70%) expressed PD-L2, whereas B2 cells and T cells failed to do so (Fig. 1A). A smaller and less distinct population of splenic B1 cells also expressed PD-L2. To exclude the possibility of staining artifacts, we sorted PD-L2 + and PD-L2 -periton...

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B-1a and B-1b Cells Exhibit Distinct Developmental Requirements and Have Unique Functional Roles in Innate and Adaptive Immunity to S. pneumoniae

Cited by 525 publications

References 31 publications

Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines

Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines

TLR Agonists Selectively Promote Terminal Plasma Cell Differentiation of B Cell Subsets Specialized in Thymus-Independent Responses

PD‐L2 expression extends beyond dendritic cells/macrophages to B1 cells enriched for V_H11/V_H12 and phosphatidylcholine binding

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B-1a and B-1b Cells Exhibit Distinct Developmental Requirements and Have Unique Functional Roles in Innate and Adaptive Immunity to S. pneumoniae

Cited by 525 publications

References 31 publications

Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines

Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines

TLR Agonists Selectively Promote Terminal Plasma Cell Differentiation of B Cell Subsets Specialized in Thymus-Independent Responses

PD‐L2 expression extends beyond dendritic cells/macrophages to B1 cells enriched for VH11/VH12 and phosphatidylcholine binding

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PD‐L2 expression extends beyond dendritic cells/macrophages to B1 cells enriched for V_H11/V_H12 and phosphatidylcholine binding