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In addition to exocrine gland dysfunction, pSD patients exhibit B cell hyperactivity. B cell\u2013intrinsic TLR7 activation is integral to the pathogenesis of systemic lupus erythematosus, a disease that shares similarities with pSD. The role of TLR7-mediated B cell activation in pSD, however, remains poorly understood. We hypothesized that age-associated B cells (ABCs) were expanded in pSD and that TLR7-stimulated ABCs exhibited pathogenic features characteristic of disease. Our data revealed that ABC expansion and TLR7 expression were enhanced in a pSD mouse model in a Myd88-dependent manner. Splenocytes from pSD mice showed enhanced sensitivity to TLR7 agonism as compared with those derived from control animals. Sort-purified marginal zone B cells and ABCs from pSD mice showed enhanced inflammatory cytokine secretion and were enriched for antinuclear autoantibodies following TLR7 agonism. Finally, IgG from pSD patient sera showed elevated antinuclear autoantibodies, many of which were secreted preferentially by TLR7-stimulated murine marginal zone B cells and ABCs. These data indicate that pSD B cells are hyperresponsive to TLR7 agonism and that TLR7-activated B cells contribute to pSD through cytokine and autoantibody production. Thus, therapeutics that target TLR7 signaling cascades in B cells may have utility in pSD patients.<\/jats:p>","DOI":"10.1093\/jleuko\/qiad135","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T11:26:57Z","timestamp":1699270017000},"page":"497-510","source":"Crossref","is-referenced-by-count":22,"title":["TLR7 activation of age-associated B cells mediates disease in a mouse model of primary Sj\u00f6gren's disease"],"prefix":"10.1093","volume":"115","author":[{"given":"Achamaporn","family":"Punnanitinont","sequence":"first","affiliation":[{"name":"Department of Oral Biology, School of Dental Medicine, University at Buffalo, State University of New York , 3435 Main Street, 520 Biomedical Research Building, Buffalo, NY 14214 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen M","family":"Kasperek","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, School of Dental Medicine, University at Buffalo, State University of New York , 3435 Main Street, 520 Biomedical Research Building, Buffalo, NY 14214 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengsong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Microarray and Immune Phenotyping Core Facility, Department of Immunology, University of Texas Southwestern Medical Center , EB3.216 Biocenter (East Campus), 2330, Inwood Rd., Dallas TX 75235 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health and Health Professions, University at Buffalo, State University of New York , 3435 Main Street, 705 Kimble Tower, Buffalo, NY 14214 , United States"},{"name":"Department of Biostatistics, School of Public Health, University of Pittsburgh , A726 Public Health, 130 DeSoto Street, Pittsburgh, PA 15261 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey C","family":"Miecznikowski","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health and Health Professions, University at Buffalo, State University of New York , 3435 Main Street, 705 Kimble Tower, Buffalo, NY 14214 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9828-8556","authenticated-orcid":false,"given":"Jill M","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, School of Dental Medicine, University at Buffalo, State University of New York , 3435 Main Street, 520 Biomedical Research Building, Buffalo, NY 14214 , United 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