9/12/2023 0 Comments Antibody repertoire microbiome![]() Innate and adaptive immunity cooperate flexibly to maintain host-microbiota mutualism. Influence of the microbiota on vaccine effectiveness. Immunogenicity and efficacy of oral vaccines in developing countries: lessons from a live cholera vaccine. Re-utilization of germinal centers in multiple Peyer’s patches results in highly synchronized, oligoclonal, and affinity-matured gut IgA responses. Hypermutation, diversity and dissemination of human intestinal lamina propria plasma cells. B cell receptor signal strength determines B cell fate. Characteristics of IgV H genes used by human intestinal plasma cells from childhood. Uncoupling of invasive bacterial mucosal immunogenicity from pathogenicity. Natural polyreactive IgA antibodies coat the intestinal microbiota. Restricted IgA repertoire in both B-1 and B-2 cell-derived gut plasmablasts. How antibodies use complement to regulate antibody responses. Role of complement in induction of antibody production in vivo: effect of cobra factor and other C3-reactive agents on thymus-dependent and thymus-independent antibody responses. Commensal microbes induce serum IgA responses that protect against polymicrobial sepsis. Microbial symbionts regulate the primary Ig repertoire. Gut microbiota-induced immunoglobulin G controls systemic infection by symbiotic bacteria and pathogens. ![]() The maternal microbiota drives early postnatal innate immune development. Maternal IgG and IgA antibodies dampen mucosal T helper cell responses in early life. High frequency of shared clonotypes in human B cell receptor repertoires. Diversity in the CDR3 region of V H is sufficient for most antibody specificities. Bacteremia associated with toothbrushing and dental extraction. Bacterial translocation from the gastrointestinal tract. Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Diversification of memory B cells drives the continuous adaptation of secretory antibodies to gut microbiota. Age, microbiota, and T cells shape diverse individual IgA repertoires in the intestine. This shows a contrast between a flexible response to systemic exposure with the need to avoid fatal sepsis, and a restricted response to mucosal exposure that reflects the generic nature of host–microbial mutualism in the mucosa. Whereas sequential systemic exposure to different microbial taxa diversified the IgG repertoire and facilitated alternative specific responses, sequential mucosal exposure produced limited overlapping repertoires and the attrition of initial IgA binding specificities. These microbial exposures induced characteristic immunoglobulin heavy-chain repertoires in B cells, mainly at memory and plasma cell stages. The IgA repertoire-predominantly to cell-surface antigens-did not expand after dose escalation, whereas increased systemic exposure broadened the IgG repertoire to both microbial cytoplasmic and cell-surface antigens. Microbial exposures at the intestinal mucosa generated oligoclonal responses that differed from those of germ-free mice, and from the diverse repertoire that was generated after intravenous systemic exposure to microbiota. We followed the development of the immunoglobulin repertoire in B cell populations, as well as single cells by deep sequencing. Here we use a simplified model of defined transient exposures to different microbial taxa in germ-free mice 3 to deconstruct how the microbiota shapes the B cell pool and its functional responsiveness. Colonization by the microbiota causes a marked stimulation of B cells and induction of immunoglobulin, but mammals colonized with many taxa have highly complex and individualized immunoglobulin repertoires 1, 2.
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