title: Innate and Adaptive Humoral Responses Coat Distinct Commensal Bacteria with Immunoglobulin A.
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.
authors: Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors: Jeffrey J
authors: JJ
authors: Bunker
authors: Biosciences Division, Argonne National Laboratory, Argonne, IL 60439, USA; Computation Institute, University of Chicago, Chicago, IL 60637, USA.
authors: Theodore M
authors: TM
authors: Flynn
authors: Biosciences Division, Argonne National Laboratory, Argonne, IL 60439, USA.
authors: Jason C
authors: JC
authors: Koval
authors: Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors: Dustin G
authors: DG
authors: Shaw
authors: Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors: Marlies
authors: M
authors: Meisel
authors: Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors: Benjamin D
authors: BD
authors: McDonald
authors: Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors: Isabel E
authors: IE
authors: Ishizuka
authors: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors: Alexander L
authors: AL
authors: Dent
authors: Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors: Patrick C
authors: PC
authors: Wilson
authors: Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors: Bana
authors: B
authors: Jabri
authors: Biosciences Division, Argonne National Laboratory, Argonne, IL 60439, USA; Computation Institute, University of Chicago, Chicago, IL 60637, USA; Department of Medicine, University of Chicago, Chicago, IL 60637, USA; Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL 60637, USA.
authors: Dionysios A
authors: DA
authors: Antonopoulos
authors: Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Pathology, University of Chicago, Chicago, IL 60637, USA. Electronic address: abendela@bsd.uchicago.edu.
authors: Albert
authors: A
authors: Bendelac
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001419:Bacteria / Q000145:classification / Q000235:genetics / Q000276:immunology*; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D005434:Flow Cytometry; D014644:Genetic Variation / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D007070:Immunoglobulin A / Q000276:immunology* / Q000378:metabolism; D007421:Intestine, Small / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D007070:Immunoglobulin A; D012336:RNA, Ribosomal, 16S