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B cell superantigens in the human intestinal microbiota.
- Source :
-
Science translational medicine [Sci Transl Med] 2019 Aug 28; Vol. 11 (507). - Publication Year :
- 2019
-
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.<br /> (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Subjects :
- Animals
Clostridiales metabolism
Enzyme-Linked Immunosorbent Assay
Firmicutes metabolism
Flow Cytometry
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
B-Lymphocytes immunology
Gastrointestinal Microbiome physiology
Superantigens immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1946-6242
- Volume :
- 11
- Issue :
- 507
- Database :
- MEDLINE
- Journal :
- Science translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 31462512
- Full Text :
- https://doi.org/10.1126/scitranslmed.aau9356