Many of the IgA producing plasma cells in murine gut are derived from self-replenishing precursors in the peritoneal cavity

Kroese, Frans G. M.; Butcher, Eugene C.; Stall, Alan M.; Lalor, Paul A.; Adams, Sharon; Herzenberg, Leonore A.

doi:10.1093/intimm/1.1.75

Cited by 335 publications

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“…Evidence for the contribution of B-1 cells to the intestinal B-cell compartment is several-fold [6,10,26]. However, due to the complexity of the cell markers to distinguish particular B-cell subpopulations, the evidences provided thus far should not yet be considered conclusive.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

“…Peritoneal cavity (PEC) B-1 cells have also been claimed to contribute significantly to IgA-producing plasma cell (PC) pool in the lamina propria (LP) of the gut [6,10,11]. Importantly, according to phenotype, origin, and function, PEC B-1 cells can be divided into B-1a and B-1b subpopulations [12,13].…”

Section: Introductionmentioning

confidence: 99%

B‐1‐cell subpopulations contribute differently to gut immunity

et al. 2013

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“…As such, the B cells in the PP that are secreting IgA are mostly in the process of migration and do not accumulate at this inductive site. Alternatively, the population of B cells responsible for the elevated numbers of IgA ASC in the LP of pIgR Ϫ/Ϫ mice could be B-1 cells derived from the peritoneal cavity, which normally constitute approximately half the IgA PC in the LP of mice (33,34). Significantly, B-1 cells are virtually absent from the PP (35).…”

Section: Discussionmentioning

confidence: 99%

Role of the Polymeric Ig Receptor in Mucosal B Cell Homeostasis

Uren

Johansen

Wijburg

et al. 2003

The Journal of Immunology

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Secretory IgA (SIgA) is the most characteristic component of the mucosal immune system and has long been considered the major protective factor that prevents pathogens from invading hosts through the mucosae. Recent studies, however, have suggested that complete immunity against a range of mucosal bacterial and viral pathogens can be achieved in the absence of IgA. Therefore, to further dissect the role of SIgA, we generated mice deficient in the polymeric Ig receptor (pIgR−/− mice). As a result of an inability to transport dimeric IgA to the secretions, pIgR−/− mice are deficient in SIgA and accumulate circulating dimeric IgA, with serum levels 100-fold greater than those observed in normal mice. Examination of lamina propria mononuclear cells showed that pIgR−/− mice had ∼3 times as many IgA-secreting cells as C57BL/6 mice. Further analysis showed that these cells displayed the differentiated IgA+ B220− phenotype and accounted for a 2-fold increase in the number of lamina propria blast cells in the pIgR−/− mice. Subsequent experiments showed that OVA-specific CD4+ T cell expansion following OVA feeding was not elevated in pIgR−/− mice. Furthermore, no differences in CD8+ T cell tolerance or induction of influenza virus-specific CD8+ T cells were detected in pIgR−/− mice compared with controls. Therefore, while SIgA is clearly involved in maintaining some parameters of mucosal homeostasis in the intestine, the mechanisms associated with its barrier function and the clinical consequences of its deficiency are yet to be identified.

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“…To separate B cell subsets to B-1 and B-2 cells (17,19), lymphocytes from different tissues were incubated with FITC-conjugated anti-IgD (PharMingen, 11-26c.2a) and PE-conjugated anti-IgM (IgH-6 b ; PharMingen, AF6-78) for the IL-15-induced B cell-proliferation assay. FITC-conjugated anti-IgA (PharMingen, R5-140), PE-conjugated anti-CD45R/B220 (PharMingen, RA3-6B2), and biotinylated anti-IgM (PharMingen, AF6-78) followed by streptavidin-conjugated PerCP (Becton Dickinson, Sunnyvale, CA) were used for the separation of sIgM ϩ sIgA Ϫ or sIgA ϩ B-1 and B-2 cells for the analysis of IL-15R and C␣ expressions and IgA production (14, 16, 17, 28 -30).…”

Section: Analysis and Purification Of B Cell Subsets By Flow Cytometrymentioning

confidence: 99%

IL-15 and IL-15 Receptor Selectively Regulate Differentiation of Common Mucosal Immune System-Independent B-1 Cells for IgA Responses

Hiroi

Yanagita

Ohta

et al. 2000

The Journal of Immunology

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We show in this report a new regulatory role for IL-15 and IL-15R in the development of B-1 cells and their differentiation into IgA-producing cells. Mucosal IgA levels were found to be inhibited by anti-IL-15 mAb treatment in vivo, but enhanced by administration of rIL-15, while serum IgA levels remained unaffected. Mucosal B-1 cells preferentially proliferated in response to IL-15 in vitro. When mucosal B-1 and B-2 cells were separated into surface (s)IgM+sIgA− and sIgM−sIgA+ fractions, IL-15R-specific mRNA was found to be predominant in both sIgM+sIgA− and sIgM−sIgA+ B-1 cells at a much higher level than B-2 cells. Further, incubation of these different subsets of B-1 and B-2 cells with IL-15 resulted in greater enhancement of the corresponding receptor expression by B-1 subset when compared with B-2 fraction. Interestingly, de novo isolated sIgM+sIgA− B-1, but not sIgM+sIgA− B-2, cells were already class-switched cells because the germline Cα transcript was detected and was then further enhanced by IL-15. IL-15 also supported differentiation of both sIgM+sIgA− and sIgM−sIgA+ B-1 cells into IgA-producing cells. Taken together, these findings suggest that IL-15 is a critically important cytokine for the differentiation of both sIgM+,IgA− and sIgM−sIgA+ B-1 cells expressing IL-15R into IgA-producing cells in mucosal tissues.

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Many of the IgA producing plasma cells in murine gut are derived from self-replenishing precursors in the peritoneal cavity

Cited by 335 publications

References 0 publications

B‐1‐cell subpopulations contribute differently to gut immunity

B‐1‐cell subpopulations contribute differently to gut immunity

Role of the Polymeric Ig Receptor in Mucosal B Cell Homeostasis

IL-15 and IL-15 Receptor Selectively Regulate Differentiation of Common Mucosal Immune System-Independent B-1 Cells for IgA Responses

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