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In VHHGAC39 TG mice, GlcNAc-reactive B-1 B cell development during ontogeny and in adult bone marrow was normal. However, adult TG mice exhibited a block at transitional-2 immature B cell stages, resulting in impaired allelic exclusion and accumulation of a B cell subset coexpressing endogenous Ig gene rearrangements. Similarly, VHHGAC39 B cell fitness was impeded compared with non-self-reactive VHJ558 B TG cells in competitive mixed bone marrow chimeras. Nonetheless, adult VHHGAC39 mice immunized with Streptococcus pyogenes produce anti-GlcNAc Abs. Peritoneal cavity B cells transferred from VHHGAC39 TG mice into RAG\u2212\/\u2212 mice also exhibited robust expansion and anti-GlcNAc Ab production. However, chronic treatment of young VHHGAC39 mice with GlcNAc-specific mAbs leads to lower GlcNAc-binding B cell frequencies while increasing the proportion of GlcNAc-binding B1-a cells, suggesting that Ag masking or clearance of GlcNAc Ags impedes maturation of newly formed GlcNAc-reactive B cells. Finally, BCR H chain editing promotes expression of endogenous nontransgenic BCR alleles, allowing potentially self-reactive TG B cells to escape anergy or deletion at the transitional stage of precursor B cell development. Collectively, these observations indicate that GlcNAc-reactive B cell development is sensitive to the access of autologous Ags.<\/jats:p>","DOI":"10.4049\/jimmunol.2300587","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T13:39:21Z","timestamp":1713793161000},"page":"1913-1921","source":"Crossref","is-referenced-by-count":4,"title":["Glycan-Reactive Innate-like B Cells and Developmental Checkpoints"],"prefix":"10.1093","volume":"212","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2034-2353","authenticated-orcid":false,"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\/0000-0003-2569-2560","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"}]},{"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"}]}],"member":"286","published-online":{"date-parts":[[2024,4,22]]},"reference":[{"key":"2025020405512192300_r1","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1002\/eji.1830270635","article-title":"The repertoire of serum IgM in normal mice is largely independent of external antigenic contact","volume":"27","author":"Haury","year":"1997","journal-title":"Eur. 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