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 hostвЂ“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 BВ cell pool and its functional responsiveness. Colonization by the microbiota causes a marked stimulation of BВ cells and induction of immunoglobulin, but mammals colonized with many taxa have highly complex and individualized immunoglobulin repertoires 1, 2.

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