Innate and Adaptive Humoral Responses Coat Distinct Commensal Bacteria with Immunoglobulin A

Jeffrey J. Bunker, Theodore M. Flynn, Jason C. Koval, Dustin G. Shaw, Marlies Meisel, Benjamin D. McDonald, Isabel E. Ishizuka, Alexander L. Dent, Patrick C. Wilson, Bana Jabri, Dionysios A. Antonopoulos, Albert Bendelac

Research output: Contribution to journalArticle

190 Scopus citations

Abstract

Immunoglobulin A (IgA) is prominently secreted at mucosal surfaces and coats a fraction of the intestinal microbiota. However, the commensal bacteria bound by IgA are poorly characterized and the type of humoral immunity they elicit remains elusive. We used bacterial flow cytometry coupled with 16S rRNA gene sequencing (IgA-Seq) in murine models of immunodeficiency to identify IgA-bound bacteria and elucidate mechanisms of commensal IgA targeting. We found that residence in the small intestine, rather than bacterial identity, dictated induction of specific IgA. Most commensals elicited strong T-independent (TI) responses that originated from the orphan B1b lineage and from B2 cells, but excluded natural antibacterial B1a specificities. Atypical commensals including segmented filamentous bacteria and Mucispirillum evaded TI responses but elicited T-dependent IgA. These data demonstrate exquisite targeting of distinct commensal bacteria by multiple layers of humoral immunity and reveal a specialized function of the B1b lineage in TI mucosal IgA responses.

Original languageEnglish (US)
Article number3150
Pages (from-to)541-553
Number of pages13
JournalImmunity
Volume43
Issue number3
DOIs
StatePublished - Sep 15 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Bunker, J. J., Flynn, T. M., Koval, J. C., Shaw, D. G., Meisel, M., McDonald, B. D., Ishizuka, I. E., Dent, A. L., Wilson, P. C., Jabri, B., Antonopoulos, D. A., & Bendelac, A. (2015). Innate and Adaptive Humoral Responses Coat Distinct Commensal Bacteria with Immunoglobulin A. Immunity, 43(3), 541-553. [3150]. https://doi.org/10.1016/j.immuni.2015.08.007