Research ArticleMICROBIOTA

B cell superantigens in the human intestinal microbiota

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Science Translational Medicine  28 Aug 2019:
Vol. 11, Issue 507, eaau9356
DOI: 10.1126/scitranslmed.aau9356

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Bacterial superantigens spur IgA secretion

Mucosal IgA is abundant and interacts with the gut microbiome. To examine microbial induction of IgA in humans, Bunker et al. screened microbiota from infants against mouse and human IgA. Unexpectedly, they saw a subset of samples bound IgA in a way that indicated the presence of superantigens, which bind T cell receptors or B cell receptors outside of the typical antigen-binding region, leading to nonspecific activation. Putative superantigens were identified in commensal members of Lachnospiraceae, which activated human VH3-positive B cells and induced IgA production in mice. These data identify commensal superantigens and suggest that they may be dominant forces behind IgA production in humans.

Abstract

IgA is prominently secreted at mucosal surfaces and coats a fraction of the commensal microbiota, a process that is critical for intestinal homeostasis. However, the mechanisms of IgA induction and the molecular targets of these antibodies remain poorly understood, particularly in humans. Here, we demonstrate that microbiota from a subset of human individuals encode two protein “superantigens” expressed on the surface of commensal bacteria of the family Lachnospiraceae such as Ruminococcus gnavus that bind IgA variable regions and stimulate potent IgA responses in mice. These superantigens stimulate B cells expressing human VH3 or murine VH5/6/7 variable regions and subsequently bind their antibodies, allowing these microbial organisms to become highly coated with IgA in vivo. These findings demonstrate a previously unappreciated role for commensal superantigens in host-microbiota interactions. Furthermore, as superantigen-expressing strains show an uneven distribution across human populations, they should be systematically considered in studies evaluating human B cell responses and microbiota during homeostasis and disease.

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