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Here we show that continuous expression of the chemokine receptor CXCR4 in Treg cells is required for their ability to accumulate in the bone marrow (BM). Induced CXCR4 ablation in Treg cells led to their rapid depletion and consequent increase in mature B cells, foremost the B-1 subset, observed exclusively in the BM without detectable changes in plasma cells or hematopoietic stem cells or any signs of systemic or local immune activation elsewhere. Dysregulation of BM B-1 B cells was associated with a highly specific increase in IgM autoantibodies and total serum IgM levels. Thus, Treg cells control autoreactive B-1 B cells in a CXCR4-dependent manner. These findings have significant implications for understanding the regulation of B cell autoreactivity and malignancies.<\/jats:p>","DOI":"10.1084\/jem.20220047","type":"journal-article","created":{"date-parts":[[2022,5,21]],"date-time":"2022-05-21T02:21:04Z","timestamp":1653099664000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["CXCR4+ Treg cells control serum IgM levels and natural IgM autoantibody production by B-1 cells in the bone marrow"],"prefix":"10.1084","volume":"219","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5055-5317","authenticated-orcid":true,"given":"Shlomo","family":"Elias","sequence":"first","affiliation":[{"name":"Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 1"},{"name":"Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8805-9431","authenticated-orcid":true,"given":"Rahul","family":"Sharma","sequence":"additional","affiliation":[{"name":"Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9285-6951","authenticated-orcid":true,"given":"Michael","family":"Schizas","sequence":"additional","affiliation":[{"name":"Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 1"},{"name":"Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8652-7043","authenticated-orcid":true,"given":"Izabella","family":"Valdez","sequence":"additional","affiliation":[{"name":"Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 1"},{"name":"Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7473-4144","authenticated-orcid":true,"given":"Sham","family":"Rampersaud","sequence":"additional","affiliation":[{"name":"Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 1"},{"name":"Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2370-0432","authenticated-orcid":true,"given":"Sun-Mi","family":"Park","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8270-552X","authenticated-orcid":true,"given":"Paula","family":"Gonzalez-Figueroa","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7257-0489","authenticated-orcid":true,"given":"Quan-Zhen","family":"Li","sequence":"additional","affiliation":[{"name":"Microarray and Immune Phenotyping Core Facility, Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3689-2445","authenticated-orcid":true,"given":"Beatrice","family":"Hoyos","sequence":"additional","affiliation":[{"name":"Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 1"},{"name":"Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1280-2898","authenticated-orcid":true,"given":"Alexander Y.","family":"Rudensky","sequence":"additional","affiliation":[{"name":"Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 1"},{"name":"Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2022,6,7]]},"reference":[{"key":"2023072618313954800_bib1","doi-asserted-by":"publisher","first-page":"53936","DOI":"10.3791\/53936","article-title":"Murine hind limb long bone dissection and bone marrow isolation","author":"Amend","year":"2016","journal-title":"J. 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