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We report that neonatal immunization with group A Streptococcus suppresses T1D development in NOD mice by promoting clonal expansion of N-acetyl-d-glucosamine (GlcNAc)-specific B-1 B cells that recognize pancreatic \u03b2 cell\u2013derived Ags bearing GlcNAc-containing posttranslational modifications. Early exposure to Lancefield group A cell-wall carbohydrate Ags increased production of GlcNAc-reactive serum Abs and enhanced localization of innate-like GlcNAc-specific B cells to pancreatic tissue during T1D pathogenesis. We show that B-1 B cell\u2013derived GlcNAc-specific IgM engages apoptosis-associated \u03b2 cell Ags, thereby suppressing diabetogenic T cell activation. Likewise, adoptively transferring GlcNAc-reactive B-1 B cells significantly delayed T1D development in naive recipients. Collectively, these data underscore potentially protective involvement of innate-like B cells and natural Abs in T1D progression. These findings suggest that previously reported associations of reduced T1D risk after GAS infection are B cell dependent and demonstrate the potential for targeting the natural Ab repertoire in considering therapeutic strategies for T1D.<\/jats:p>","DOI":"10.4049\/jimmunol.2300264","type":"journal-article","created":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T13:26:11Z","timestamp":1695648371000},"page":"1320-1331","source":"Crossref","is-referenced-by-count":8,"title":["B-1 B Cell\u2013Derived Natural Antibodies against <i>N<\/i>-Acetyl-<scp>d<\/scp>-Glucosamine Suppress Autoimmune Diabetes Pathogenesis"],"prefix":"10.1093","volume":"211","author":[{"given":"J Stewart","family":"New","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham , Birmingham, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian L P","family":"Dizon","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham , Birmingham, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6522-0053","authenticated-orcid":false,"given":"R Glenn","family":"King","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham , Birmingham, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil S","family":"Greenspan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University , Cleveland, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2569-2560","authenticated-orcid":false,"given":"John F","family":"Kearney","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham , Birmingham, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,9,25]]},"reference":[{"key":"2025020406163591400_r1","doi-asserted-by":"crossref","first-page":"a007799","DOI":"10.1101\/cshperspect.a007799","article-title":"The hygiene hypothesis: an explanation for the increased frequency of insulin-dependent diabetes","volume":"2","author":"Bach","year":"2012","journal-title":"Cold Spring Harb. 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