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Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>B-cell activation triggers the release of endoplasmic reticulum calcium stores through the store-operated calcium entry (SOCE) pathway resulting in calcium influx by calcium release-activated calcium (CRAC) channels on the plasma membrane. B-cell-specific murine knockouts of SOCE do not impact humoral immunity suggesting that alternative channels may be important.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We identified a member of the calcium-permeable transient receptor potential (TRP) ion channel family, TRPV5, as a candidate channel expressed in B cells by a quantitative polymerase chain reaction (qPCR) screen. To further investigate the role of TRPV5 in B-cell responses, we generated a murine TRPV5 knockout (KO) by CRISPR\u2013Cas9. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found TRPV5 polarized to B-cell receptor (BCR) clusters upon stimulation in a PI3K\u2013RhoA-dependent manner. TRPV5 KO mice have normal B-cell development and mature B-cell numbers. Surprisingly, calcium influx upon BCR stimulation in primary TRPV5 KO B cells was not impaired; however, differential expression of other calcium-regulating proteins, such as ORAI1, may contribute to a compensatory mechanism for calcium signaling in these cells. We demonstrate that TRPV5 KO B cells have impaired spreading and contraction in response to membrane-bound antigen. Consistent with this, TRPV5 KO B cells have reduced BCR signaling measured through phospho-tyrosine residues. Lastly, we also found that TRPV5 is important for early T-dependent antigen specific responses post-immunization. <\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Thus, our findings identify a role for TRPV5 in BCR signaling and B-cell activation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1386719","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T04:36:36Z","timestamp":1713328596000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["The ion channel TRPV5 regulates B-cell signaling and activation"],"prefix":"10.3389","volume":"15","author":[{"given":"Trisha","family":"Mahtani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hena","family":"Sheth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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