B cell superantigens in the human intestinal microbiota

Sci Transl Med. 2019 Aug 28;11(507):eaau9356. doi: 10.1126/scitranslmed.aau9356.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Clostridiales / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Firmicutes / metabolism
  • Flow Cytometry
  • Gastrointestinal Microbiome / physiology*
  • Humans
  • Lacticaseibacillus rhamnosus / metabolism
  • Listeria monocytogenes / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NOD
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism
  • Ruminococcus / metabolism
  • Superantigens / immunology*


  • Myeloid Differentiation Factor 88
  • Superantigens

Supplementary concepts

  • Coprococcus comes
  • Dorea formicigenerans
  • Erysipelatoclostridium ramosum