B1b Lymphocytes Confer T Cell-Independent Long-Lasting Immunity

Alugupalli, Kishore R.; Leong, John M.; Woodland, Robert T.; Muramatsu, Masamichi; Honjo, Tasuku; Gerstein, Rachel M.

doi:10.1016/j.immuni.2004.06.019

Cited by 365 publications

(449 citation statements)

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“…B. hermsii-specific IgM induced by the bacteremia is capable of clearing the vmp-expressing spirochete population from the host (4). B1b cells are one source of B. hermsii-specific IgM that can control low dose bacteremia associated with attenuated (high passage) B. hermsii variants, as has been shown using xid mice, which are deficient in the B1b cell subset (6). However, Ab produced by these cells is less effective in clearing virulent (low passage) B. hermsii (5).…”

Section: Discussionmentioning

confidence: 98%

“…These findings underscore the importance of pathogen-specific IgM in the clearance of Borrelia spirochetes and suggest that B cell subsets other than follicular B cells contribute to protective immunity against infection with these organisms. In this regard, the B1b cell subset has been shown to be a source of protective Ab against B. hermsii, but only after priming by infection (6). Naive B1b cells, in contrast, produce Ab that can clear attenuated (high passage) B. hermsii, but are unable to clear the first episode of spirochetemia in primary infection of mice with virulent (low passage) B. hermsii (6).…”

mentioning

confidence: 99%

“…In this regard, the B1b cell subset has been shown to be a source of protective Ab against B. hermsii, but only after priming by infection (6). Naive B1b cells, in contrast, produce Ab that can clear attenuated (high passage) B. hermsii, but are unable to clear the first episode of spirochetemia in primary infection of mice with virulent (low passage) B. hermsii (6). Together these findings suggest that other B cell subsets, such as marginal zone B (MZB) cells, may be an additional source of early protective Ab against B. hermsii.…”

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confidence: 99%

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Infection-Induced Marginal Zone B Cell Production of Borrelia hermsii-Specific Antibody Is Impaired in the Absence of CD1d

Belperron

Dailey

Bockenstedt

2005

The Journal of Immunology

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Ab that arise in the absence of T cell help are a critical host defense against infection with the spirochetes Borrelia burgdorferi and Borrelia hermsii. We have previously shown that CD1d-deficient (CD1d−/−) mice have impaired resistance to infection with B. burgdorferi. In mice, CD1d expression is highest on marginal zone B (MZB) cells, which produce Ab to blood-borne Ag. In this study we examined MZB cell activation and Ab production in mice infected with B. hermsii, which achieve high levels of bacteremia. We show by flow cytometry that MZB cells associate with B. hermsii and up-regulate the activation markers syndecan I and B7.1 within 16 h of infection. By 24 h, MZB cells secrete B. hermsii-specific IgM, coinciding with the loss of activation marker expression and the reduction in spirochete burden. In contrast, MZB cells from CD1d−/− mice remain activated for at least 96 h of infection, but produce only minimal B. hermsii-specific IgM in vivo and ex vivo; pathogen burden in the blood also remains elevated. Wild-type mice depleted of MZB cells using mAb to LFA-1 and α4β1 integrin have reduced serum levels of B. hermsii-specific IgM and increased pathogen burden, similar to B. hermsii-infected CD1d−/− mice. Passive transfer of immune mouse serum, but not naive mouse serum, into infected CD1d−/− mice leads to down-regulation of activation markers and clearance of B. hermsii from the MZB cells. These results demonstrate that blood-borne spirochetes activate MZB cells to produce pathogen-specific IgM and reveal a role for CD1d in this process.

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Section: Discussionmentioning

confidence: 98%

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confidence: 99%

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confidence: 99%

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Infection-Induced Marginal Zone B Cell Production of Borrelia hermsii-Specific Antibody Is Impaired in the Absence of CD1d

Belperron

Dailey

Bockenstedt

2005

The Journal of Immunology

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“…[5][6][7]. However, the precise contribution of T-cell-dependent and TI pathways to IgA production is not known.An important contribution of B-1 cells to TI responses has been suggested [6,8,9]. Peritoneal cavity (PEC) B-1 cells have also been claimed to contribute significantly to IgA-producing plasma cell (PC) Eur.…”

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confidence: 99%

B‐1‐cell subpopulations contribute differently to gut immunity

et al. 2013

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IntroductionIgA is the major class of Ab present in mucosal tissues of mammals. IgA constitutes a key defense mechanism against invasion by inhaled or ingested pathogens. IgA is also found at significant concentrations in the serum of many species, where it mediates the elimination of pathogens that have breached the mucosa [1].Among the various MALTs, IgA-producing cells are present in highest numbers in GALTs constituted by Peyer's patches (PPs), isolated lymphoid follicles (ILFs), and solitary intestinal lymphoid Correspondence: Dr. Bishnudeo Roy e-mail: Bishnudeo.Roy@helmholtz-hzi.de tissue (SILT) [2,3]. B cells, present in the B-cell follicles of such organized structures, form GCs upon Ag encounter. Under the influence of various cellular and molecular factors -T cells and cytokines, for instance -these B cells are thought to switch from IgM to IgA [4].Multiple pathways of IgA induction have been reported. The T-cell-dependent pathway of IgA induction is well known and, it is clear that IgA can also be induced in T-cell-independent (TI) manner (e.g. in T-cell-deficient mice, CD40 −/− mice, CD28 −/− mice, etc.) [5][6][7]. However, the precise contribution of T-cell-dependent and TI pathways to IgA production is not known.An important contribution of B-1 cells to TI responses has been suggested [6,8,9]. Peritoneal cavity (PEC) B-1 cells have also been claimed to contribute significantly to IgA-producing plasma cell (PC) Eur. J. Immunol. 2013Immunol. . 43: 2023Immunol. -2032. Importantly, according to phenotype, origin, and function, PEC B-1 cells can be divided into B-1a and B-1b subpopulations [12,13]. Phenotypically, B-1a cells are characterized as B220 lo CD19 hi IgM hi IgD lo CD43 + Mac-1 + CD5 int . B-1b cells share all the aforementioned markers with B-1a cells except CD5. With respect to differential contribution of these two B-1-cell subtypes to IgA production, recently, we could show that most of the IgA-secreting cells in the PEC of unmanipulated mice belonged to B-1b-cell subpopulation [14]. Additionally, IgA-derived VH regions from B-1b cells also contained frequent single nucleotide exchanges indicative of somatic hypermutation (SHM) [14]. Thus, a contribution of PEC B-1b cells to IgA production and hence to gut-associated immunity is quite likely. However, in spite of evidential suggestions for the contribution of B-1 cells to the intestinal PC pool, their contribution under unmanipulated conditions remains uncertain. This is partly due to the lack of appropriate markers to distinguish PCs according to their origin. In this context, a sequence-based approach to address this question should become very useful.In the present work, to investigate the participation of PEC B-1 cells in the gut-associated IgA production we have made use of the transgenic mouse model known as the L2 mouse line [15]. Mice of this line are characterized by the expression of a transgenic λ light chain obtained from the plasmacytoma MOPC315 (λ2 315 ). PEC of these mice contains almost exclusively CD5 + B-1a cells, whi...

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“…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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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

264

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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B1b Lymphocytes Confer T Cell-Independent Long-Lasting Immunity

Cited by 365 publications

References 38 publications

Infection-Induced Marginal Zone B Cell Production of Borrelia hermsii-Specific Antibody Is Impaired in the Absence of CD1d

Infection-Induced Marginal Zone B Cell Production of Borrelia hermsii-Specific Antibody Is Impaired in the Absence of CD1d

B‐1‐cell subpopulations contribute differently to gut immunity

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

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