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Anti-insulin germinal center B cells are uniquely able to present pathogenic insulin epitopes and drive anti-insulin T cells to adopt a T follicular helper fate. T cell expression of BCL6, a key transcriptional repressor in the germinal center response, is essential for spontaneous diabetes in non-obese diabetic (NOD) mice. However, the impact of T cells on pro-pathogenic anti-insulin B cell activity is still poorly understood. Here, we show that VH125\n                  <jats:sup>SD<\/jats:sup>\n                  .NOD mice with T cell loss of BCL6 still produce peripheral anti-insulin B cells yet are protected against diabetes (relative to\n                  <jats:italic>Bcl6<\/jats:italic>\n                  -sufficient controls). This protection was associated with reduced activation, proliferation, germinal center differentiation, and pancreatic infiltration of insulin-binding B cells. Minimally supervised analysis revealed insulin-binding B cells skew towards atypical memory B cell subsets specifically in pancreas and pancreatic lymph nodes, which was reduced by\n                  <jats:italic>Bcl6<\/jats:italic>\n                  <jats:sup>\n                    \u0394\n                    <jats:italic>CD4<\/jats:italic>\n                  <\/jats:sup>\n                  loss. Overall, this work suggests BCL6-expressing T cells are pivotal to license pathogenic insulin-binding B cells. Our findings support BCL6 inhibition as a promising T1D immunotherapy, even after insulin autoimmunity is established in the B cell repertoire.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Article Highlights<\/jats:title>\n                  <jats:list list-type=\"simple\">\n                    <jats:list-item>\n                      <jats:p>\n                        - Loss of floxed\n                        <jats:italic>Bcl6<\/jats:italic>\n                        via\n                        <jats:italic>Cd4<\/jats:italic>\n                        -Cre protects against type 1 diabetes even when an insulin-skewed B cell repertoire is present\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        - BCL6 loss in T cells reduces anti-insulin B cell upregulation of T cell co-stimulatory molecules, proliferation, and IgG class switching in pancreas and pancreatic lymph nodes in VH125\n                        <jats:sup>SD<\/jats:sup>\n                        .NOD mice\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        - Anti-insulin B cells skew towards atypical and atypical memory B cell phenotypes compared to non-insulin binding B cells in pancreas and pancreatic lymph nodes, only some of which are reduced by T cell loss of\n                        <jats:italic>Bcl6<\/jats:italic>\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>- This study highlights the translational potential of targeting BCL6, even after the establishment of insulin-reactive B cells, in line with typical intervention points for at-risk individuals<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"671997v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.1101\/2025.08.25.671997","type":"posted-content","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T01:10:25Z","timestamp":1756429825000},"source":"Crossref","is-referenced-by-count":0,"title":["BCL6 in T cells promotes type 1 diabetes by redirecting fates of insulin-autoreactive B lymphocytes"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1537-4692","authenticated-orcid":false,"given":"Landon 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E.","family":"Bass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5470-9558","authenticated-orcid":false,"given":"Casey M.","family":"Nichols","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4106-3396","authenticated-orcid":false,"given":"Jeffrey C.","family":"Rathmell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7575-6943","authenticated-orcid":false,"given":"Rachel 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