Monoclonal immunoglobulin A derived from peritoneal B cells is encoded by both germ line and somatically mutated VH genes and is reactive with commensal bacteria

Abstract

We transferred peritoneal cells from BALB/c mice into C.B17 scid/scid mice. Six to eight months after injection, only cells with the B1 phenotype were retained in the spleens and peritoneal cavities of these mice. The lamina propria of the intestine contained many peritoneal, donor-derived, immunoglobulin A (IgA)-producing cells. The mesenteric lymph nodes of these mice were found to be a major site of proliferation and generation of IgA plasmablasts. We established eight IgA-producing hybridomas from the mesenteric lymph nodes of such mice, and all the hybridomas reacted with different but partially overlapping fecal bacterial populations. Cloning and sequencing of the V H genes of these hybridomas showed that two hybridomas utilized germ line-encoded V H genes while the V H genes of the other six hybridomas showed somatic mutations, some of which are indicative of an antigen-driven selection process.

Immune responses that adapt the intestinal mucosa to commensal intestinal bacteria

“…63 It is has also been suggested that B 1 class switch recombination may take place in the mesenteric lymph nodes. 48,64 We found that significant intestinal IgA only occurred in strains with some B-cell structures in the intestine, although these could be very disorganized, for example without follicular dendritic cells and germinal centres in mice deficient for the TNF receptor I. 42,65 Regardless of relative B 1 /B 2 contributions, the IgA response has a restricted V H repertoire of intestinal immunoglobulin a heavy chains in mouse 48 and man.…”

Specific antibody activity, glycan heterogeneity and polyreactivity contribute to the protective activity of S-IgA at mucosal surfaces

“…Bacteria 0165-2478/$ -see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.imlet.2009.03.013 Table 1 Examples of glycans as adhesion sites and receptors for selected bacteria and viruses that colonize, or infect, mucosal surfaces (adapted from [1,26,29,[60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78]132] endogenous to the intestinal tract, oral cavity, and probably also the respiratory and genital tracts, are coated in vivo with S-IgA [9,13,17,[31][32][33][34][35][36][37][38][39] that limits their epithelial adherence and penetration, thereby confining them to the mucosal surfaces. Numerous models have demonstrated the role of antibodies, especially S-IgA, in protecting the intestinal and other mucosal tracts.…”

“…This concept, of paramount importance in IgA-mediated mucosal defense, prompts additional considerations. First, it has been shown that bacteria indigenous to the oral cavity and intestinal tract are coated in vivo with IgA [9,17,[31][32][33][34][35][36][37][38][39][79][80][81]. However, it is not known whether this coating depends on specific antibody-antigen or glycan-mediated interactions.…”

The Role of Mucosal Microbiota in the Development, Maintenance, and Pathologies of the Mucosal Immune System

“…Although we believe that B1 cells can populate the gut with IgA plasmablasts and some of these make IgA that reacts with a particular pattern of microbial Ags (Bos et al, 1996), we have so far found little substantial evidence that indicates that these cells arise by specific Ag selection and stimulation to divide and/or differentiate into secretory plasma cells. Recently, Macpherson et al (2000) have shown that TCR (−/−) mice can exhibit an antimicrobial IgA response in the gut and that a complex radiation chimera seems to express a predominance of IgA plasmablasts with the allotype of the transferred, semipurified PeC B1 cells; no specific responses were measured in the latter case.…”