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The fate of B cells at these checkpoints is believed to be regulated by intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      signaling cascades triggered through engagement of B cell receptors (BCR), and by the suppressive effects of regulatory T cells (Tregs). However, most of the current knowledge about Treg\u2013B cell interaction comes from animal studies, while data from human studies, particularly in the context of AID, are sparse. In contrast, impaired Treg-mediated inhibition of conventional T cells (Tcons) has already been described for several AID, including MS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the ability of Tregs to suppress activated B cells in healthy individuals and patients with MS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>B and T cell populations were isolated from 40 MS patients and 98 age- and sex-matched healthy donors (HD). Single-cell live Ca\u00b2\u207a imaging was used to assess early activation signals in B cells. In vitro proliferation assays and coculture experiments were employed to evaluate downstream responses, including proliferation, transcription factor activation (NFATc1, NF-\u0138B), interleukin 6 (IL-6) release, and surface expression levels of antigen-presenting capacity (APC) markers both in anti-IgM\/anti-CD40-stimulated B cells alone, and in the presence of Tregs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We demonstrate that Tregs exert a robust suppressive effect on B cell proliferation, IL-6 secretion and NFATc1 which is [1] independent of Ca\n                      <jats:sup>2+<\/jats:sup>\n                      signaling [2], dependent on direct cell contact, and [3] impaired in MS. In contrast, early Ca\n                      <jats:sup>2+<\/jats:sup>\n                      responses and downstream effects of anti-IgM\/anti-CD40 stimulation, including activation of NFATc1 and NF-\u03baB, as well as proliferation, did not differ between MS- and HD-derived B cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides new data on Treg-mediated suppression of B cells in humans, including at single-cell level. Our findings show that the Treg dysfunction in MS previously described in the context of Tcon regulation extends to B cell regulation. Given the critical role of B cells in MS pathogenesis, this impaired Treg\u2013B cell interaction may represent a previously underappreciated disease mechanism with potentially important therapeutic implications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-026-03776-5","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T05:04:51Z","timestamp":1777698291000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impaired suppressive effect of FoxP3 regulatory T cells on B cells in multiple sclerosis"],"prefix":"10.1186","volume":"23","author":[{"given":"Viktoria B.","family":"Greeck","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelia","family":"W\u00fcrthwein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karina","family":"Mimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Mattes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Kutza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas","family":"Schirmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Fairless","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah K.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Jarius","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Haas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klemens","family":"Ruprecht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brigitte","family":"Wildemann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,2]]},"reference":[{"key":"3776_CR1","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.cellimm.2017.05.007","volume":"318","author":"E Weingartner","year":"2017","unstructured":"Weingartner E, Golding A. 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Patients gave written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"V.B.G., C.W., K.M. R.F., S.K.W., J.H., M.K. and S.J. report no conflicts of interest. K.R. received research support from Novartis, Merck Serono, German Ministry of Education and Research, European Union (821283-2), Stiftung Charit\u00e9, Guthy-Jackson Charitable Foundation and Arthur Arnstein Foundation, travel grants from Guthy-Jackson Charitable Foundation, speaker\u2019s honoraria from Virion Serion and Novartis, was a participant in the BIH Clinical Fellow Program funded by Stiftung Charit\u00e9. 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