B‐1‐cell subpopulations contribute differently to gut immunity

Abstract

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...

An Intrinsic Propensity of Murine Peritoneal B1b Cells to Switch to IgA in Presence of TGF-β and Retinoic Acid

“…When tested for the reactivity against gut bacteria, secretory IgA present in the culture supernatant of PEC B cells showed their binding towards these commensals (Figure S3). This is consistent with our previous finding that showed the binding of B1 cell derived Igs to gut bacteria [28]. Furthermore, analysis of secretory IgG in the culture supernatants showed that the amount of IgG decreased to a minimum under conditions that favored the switching to IgA (Figure 2B).…”

Innate-like B cell subsets during immune responses: Beyond antibody production

“…Natural IgM secreted by these cells play tissue homeostasis‐maintaining roles due to their faculty to bind self‐antigens, such as those expressed by apoptotic cells in ischemia‐induced tissue injury and oxidized LDLs in atherosclerosis . Apart from IgM, B‐1 cells can also secrete polyreactive IgA Abs that contribute to mucosal immunity in concert with the IgA fraction secreted by FO B cells …”

Secretory IgA: Designed for Anti-Microbial Defense

“…However, the relationship of murine B1 cells to the conventional bone marrow-derived B2 cells remains elusive. Notably, rather than being encoded only in germline, B1 cells from mice may show considerable somatic hypermutation (SHM) of Ig H-chain V-region (V H ) genes as a sign of selection (122, 123). …”