The majority of intestinal IgA+ and IgG+ plasmablasts in the human gut are antigen-specific

Abstract

Mucosal antibody responses play a major role in mediating homeostasis with the intestinal flora. It has been suggested that imbalance in the IgA + and IgG + intestinal B cell repertoire may be associated with the development of diseases such as inflammatory bowel disease. Despite this, little is known about the antibody specificity of human intestinal plasmablasts. Here, we have determined the reactivity profile of single isolated IgA + and IgG + plasmablasts from human terminal ileum using antibody cloning and in vitro expression. We found that approximately 25% of intestinal IgA and IgG plasmablast antibodies were polyreactive; the majority were antigen-specific. Antigen specificity was not only directed against enteropathogenic microbes but also against commensal microbes and self antigens. Regardless of their reactivity, all intestinal antibodies were somatically mutated and showed signs of antigen-mediated selection, suggesting that they developed from antigen-specific B cell responses. Together, our data indicate that antigen-specific immune responses to intestinal microbes are largely responsible for the maintenance of intestinal homeostasis and thus provide a basis for understanding the deregulated immune responses observed in patients with inflammatory bowel disease.

Diagnostic Potential of Monoclonal Antibodies Specific to the Unique O-Antigen of Multidrug-Resistant Epidemic Escherichia coli Clone ST131-O25b:H4

“…The prototype sequenced O25a strain E. coli E47a was obtained from the NCTC. E. coli strain 509A is a human fecal isolate (18), which was confirmed by O-typing (Hungarian Epidemiology Center) to express the O2 antigen. The mouse immunization experiments (see below) were performed with an isogenic knockout mutant of the representative ST131 strain E. coli 81009 that was generated by deleting the whole kps cluster encoding capsular synthesis.…”

Characterization of proposed human B-1 cells reveals pre-plasmablast phenotype

“…28 However, this does not hold true for humans, in which intestinal IgA 1 plasmablast are generated in germinal centers 29 and carry a number of somatic hypermutations in their Ig variable regions (a hallmark of selection of follicular B-2 cells through germinal center reactions), comparable to IgG 1 plasmablasts. 30 The results of spontaneous antibody secretion by the proposed B-1 cells are at odds with the phenotype of murine B-1 cells, for which IgM is expected to be the dominant isotype produced. 1 In addition to spontaneous antibody secretion, we also found striking similarities between the proposed B-1 cells and plasmablasts with regard to antibody production induced by vaccination.…”

Characterizing the Interactions between a Naturally Primed Immunoglobulin A and Its Conserved Bacteroides thetaiotaomicron Species-specific Epitope in Gnotobiotic Mice

“…IgA responses can develop in a T cell-dependent or -independent manner (11) and may exhibit either broad or limited reactivity (12)(13)(14)(15). Although class switching and plasma cell maturation in the gut were classically described in Peyer patches, evidence suggests that these processes may also occur locally in the intestinal lamina propria in response to cues from the microbiota, epithelium, and stromal compartment (16).…”