@article{e31e15ac384e42d49ba61afa274e9418,
title = "Natural polyreactive IgA antibodies coat the intestinal microbiota",
abstract = "Large quantities of immunoglobulin A (IgA) are constitutively secreted by intestinal plasma cells to coat and contain the commensal microbiota, yet the specificity of these antibodies remains elusive. Here we profiled the reactivities of single murine IgA plasma cells by cloning and characterizing large numbers of monoclonal antibodies. IgAs were not specific to individual bacterial taxa but rather polyreactive, with broad reactivity to a diverse, but defined, subset of microbiota. These antibodies arose at low frequencies among naive B cells and were selected into the IgA repertoire upon recirculation in Peyer's patches. This selection process occurred independent of microbiota or dietary antigens. Furthermore, although some IgAs acquired somatic mutations, these did not substantially influence their reactivity. These findings reveal an endogenous mechanism driving homeostatic production of polyreactive IgAs with innate specificity to microbiota.",
author = "Bunker, {Jeffrey J.} and Erickson, {Steven A.} and Flynn, {Theodore M.} and Carole Henry and Koval, {Jason C.} and Marlies Meisel and Bana Jabri and Antonopoulos, {Dionysios A.} and Wilson, {Patrick C.} and Albert Bendelac",
note = "Funding Information: We thank the University of Chicago Flow Cytometry Core for assistance with cell sorting; S. Owens and S. Greenwald at the Argonne National Laboratory Environmental Sample Preparation and Sequencing Facility for assistance with 16S sequencing; the University of Chicago DNA Sequencing Core for assistance with plasmid minipreps and sequencing; B. Theriault and the University of Chicago Gnotobiotic Facility for assistance with germ-free and antigen-free experiments; the Consortium for Functional Glycomics for microbial glycan microarray screening; G. Salzman for assistance with fast protein liquid chromatography; and S. Canavan for assistance with figure preparation. This work was supported by NIH grants: T32GM007281 and F30AI124476 (to J.J.B.); U01AI125250, R01AI038339, R01AI108643, R01GM106173, and R01HL118092 (to A.B.); P41GM103694 to the National Center for Functional Glycomics at Beth Israel Deaconess Medical Center; and P30DK042086 to the University of Chicago Digestive Diseases Research Core Center (to A.B., B.J., and D.A.A.). J.J.B. and A.B. conceived the study; J.J.B., S.A.E., and A.B. designed research; A.B. supervised research; J.J.B. and S.A.E. performed experiments and analyzed data; C.H. and P.C.W. contributed anti-influenza mAbs and advice regarding mAb production and characterization; T.M.F., J.C.K., and D.A.A. processed samples for 16S sequencing and analyzed associated data; M.M. and B.J. provided mice and assistance with gnotobiotic experiments; J.J.B. and A.B. wrote the paper; and all authors approved the final manuscript. All data to understand and assess the conclusions of this research are available in the main text, supplementary materials, and the following repositories: GenBank, antibody sequences are available under accession numbers MF466210-MF467203, and MG-RAST, 16S rRNA sequencing data are available under accession number MGP80334.",
year = "2017",
month = oct,
day = "20",
doi = "10.1126/science.aan6619",
language = "English",
volume = "358",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6361",
}