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Although\n                    <jats:italic>TNFRSF13B<\/jats:italic>\n                    supports host defense, dominant-negative\n                    <jats:italic>TNFRSF13B<\/jats:italic>\n                    alleles are common in humans and other species and only rarely associate with disease. We reasoned that the high frequency of disruptive\n                    <jats:italic>TNFRSF13B<\/jats:italic>\n                    alleles reflects balancing selection, the loss of function conferring advantage in some settings. Testing that concept, we investigated how a common human dominant-negative variant, TNFRSF13B A181E, imparts resistance to enteric pathogens. Mice engineered to express mono- or biallelic A144E variants of\n                    <jats:italic>tnrsf13B<\/jats:italic>\n                    , corresponding to A181E, exhibited a striking resistance to pathogenicity and transmission of\n                    <jats:italic>Citrobacter rodentium<\/jats:italic>\n                    , a murine pathogen that models enterohemorrhagic\n                    <jats:italic>Escherichia<\/jats:italic>\n                    <jats:italic>coli<\/jats:italic>\n                    , and resistance was principally owed to natural IgA deficiency in the intestine. In WT mice with gut IgA and in mutant mice reconstituted with enteric IgA obtained from WT mice, IgA induces\n                    <jats:italic>LEE<\/jats:italic>\n                    expression of encoded virulence genes, which confer pathogenicity and transmission. Taken together, our results show that\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>rodentium<\/jats:italic>\n                    and most likely other enteric organisms appropriated binding of otherwise protective antibodies to signal induction of the virulence program. Additionally, the high prevalence of\n                    <jats:italic>TNFRSF13B<\/jats:italic>\n                    dominant-negative variants reflects balancing selection.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.148208","type":"journal-article","created":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T12:01:07Z","timestamp":1623326467000},"source":"Crossref","is-referenced-by-count":3,"title":["TNFRSF13B polymorphisms counter microbial adaptation to enteric IgA"],"prefix":"10.1172","volume":"6","author":[{"given":"Jeffrey L.","family":"Platt","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology and Department of Surgery,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayara Garcia","family":"de Mattos Barbosa","sequence":"additional","affiliation":[{"name":"Department of 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