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Although much progress has been made in understanding the nature of genetic underpinnings of autoimmune disease, by comparison much less is understood regarding how environmental factors interact with genetics in the development of autoimmunity and autoimmune disease. In this report, we utilize the (New Zealand black \u00d7 New Zealand white [NZB \u00d7 NZW]) F1 mouse model of systemic lupus erythematosus (SLE). Mercury is a xenobiotic that is environmentally ubiquitous and is epidemiologically linked with the development of autoimmunity. Among other attributes of human SLE, (NZB \u00d7 NZW) F1 mice spontaneously develop autoimmune-mediated kidney disease. It has been previously shown that if (NZB \u00d7 NZW) F1 mice are exposed to inorganic mercury (Hg2+), the development of autoimmunity, including autoimmune kidney pathology, is accelerated. We now show that in these mice, the development of kidney disease is correlated with a decreased percentage of marginal zone (MZ) B-cells in the spleen. In Hg2+-intoxicated mice, kidney disease is significantly augmented, and matched by a greater decrease in MZ B-cell splenic percentages than found in control mice. In Hg2+- intoxicated mice, the decrease in MZ B-cells appears to be linked to aberrant B-cell receptor signal strength in transitory 2 (T2) B-cells, developmental precursors of MZ B-cells.<\/jats:p>","DOI":"10.1093\/toxsci\/kfad120","type":"journal-article","created":{"date-parts":[[2023,11,12]],"date-time":"2023-11-12T16:20:24Z","timestamp":1699806024000},"page":"211-221","source":"Crossref","is-referenced-by-count":1,"title":["Naturally occurring autoimmune disease in (NZB \u00d7 NZW) F1 mice is correlated with suppression of MZ B-cell development due to aberrant B-cell receptor (BCR) signaling, which is exacerbated by exposure to inorganic mercury"],"prefix":"10.1093","volume":"197","author":[{"given":"Randall F","family":"Gill","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Microbiology and Immunology, Wayne State University , Detroit, Michigan 48201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia A","family":"Mathieu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Wayne State University , Detroit, Michigan 48201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3239-4481","authenticated-orcid":false,"given":"Lawrence H","family":"Lash","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Wayne State University , Detroit, Michigan 48201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allen J","family":"Rosenspire","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology and Immunology, Wayne State University , Detroit, Michigan 48201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,11,11]]},"reference":[{"key":"2024012913070926700_kfad120-B1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/BF02786508","article-title":"Murine mercury-induced autoimmunity: A model of chemically related autoimmunity in humans","volume":"20","author":"Bagenstose","year":"1999","journal-title":"Immunol. 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