AUTHOR=Bonami Rachel H. , Thurman Christina E. , Verma Sonam , Westlake Camille S. , Nyhoff Lindsay E. , Barron Bridgette B. , Reboldi Andrea , Kendall Peggy L. 

TITLE=Bruton’s Tyrosine Kinase Supports Gut Mucosal Immunity and Commensal Microbiome Recognition in Autoimmune Arthritis

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.748284

DOI=10.3389/fimmu.2022.748284

ISSN=1664-3224

ABSTRACT=<p>Bruton’s tyrosine kinase (<italic>Btk</italic>) deficiency preferentially eliminates autoreactive B cells while sparing normal humoral responses, but has not been studied in mucosal immunity. Commensal microbes and intact BTK signaling have been independently shown to be essential for arthritis development in K/BxN mice. Here, we examine how BTK-mediated signaling interfaces with the gut microbiome. <italic>Btk</italic>-deficient K/BxN mice were found to have small Peyer’s Patches with reduced germinal center and IgA class-switched B cells. IgA-switched plasma cells in small intestines were reduced, especially in villi of <italic>Btk</italic>-deficient mice. IgH CDR3 sequencing showed similar V gene diversity and somatic hypermutation frequency despite <italic>Btk</italic> deficiency but showed reduced CDR3 amino acid polarity, suggesting potential qualitative differences in the gut plasma cell repertoire. Small intestinal IgA was low and IgA coating of commensal bacteria was reduced. IgA-seq showed a shift in small intestinal microbes that are normally IgA-coated into the uncoated fraction in <italic>Btk</italic>-deficient mice. Overall, this study shows that BTK supports normal intestinal IgA development in response to commensals.</p><p>This manuscript was previously published as a preprint at: <uri xlink:href="https://www.biorxiv.org/content/10.1101/2021.03.10.434762v2" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.biorxiv.org/content/10.1101/2021.03.10.434762v2</uri>.</p>