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However, it is not known whether the positive selection of the different Ig isotypes within GCs is dependent on specific transcriptional mechanisms. Here, we explored IgG1\n            <jats:sup>+<\/jats:sup>\n            GC B cell transcription factor dependency using a CRISPR-Cas9 screen and conditional mouse genetics. We found that MIZ1 was specifically required for IgG1\n            <jats:sup>+<\/jats:sup>\n            GC B cell survival during positive selection, whereas IgM\n            <jats:sup>+<\/jats:sup>\n            GC B cells were largely independent. Mechanistically, MIZ1 induced TMBIM4, an ancestral anti-apoptotic protein that regulated inositol trisphosphate receptor (IP3R)\u2013mediated calcium (Ca\n            <jats:sup>2+<\/jats:sup>\n            ) mobilization downstream of B cell receptor (BCR) signaling in IgG1\n            <jats:sup>+<\/jats:sup>\n            B cells. The MIZ1-TMBIM4 axis prevented mitochondrial dysfunction\u2013induced IgG1\n            <jats:sup>+<\/jats:sup>\n            GC cell death caused by excessive Ca\n            <jats:sup>2+<\/jats:sup>\n            accumulation. This study uncovers a unique Ig isotype\u2013specific dependency on a hitherto unidentified mechanism in GC-positive selection.\n          <\/jats:p>","DOI":"10.1126\/sciimmunol.adk0092","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T17:58:23Z","timestamp":1712339903000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":11,"title":["Regulation of BCR-mediated Ca\n            <sup>2+<\/sup>\n            mobilization by MIZ1-TMBIM4 safeguards IgG1\n            <sup>+<\/sup>\n            GC B cell\u2013positive selection"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7423-3761","authenticated-orcid":true,"given":"Lingling","family":"Zhang","sequence":"first","affiliation":[{"name":"Immunity and Cancer, Francis Crick Institute, London, 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