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Here, we studied the B cell response in an autoantigen\u2010 and CD4<jats:sup>+<\/jats:sup> T cell\u2010driven model of autoimmune hepatitis (AIH), the Alb\u2010iGP_Smarta mouse in which expression of a viral model antigen (GP) in hepatocytes and its recognition by GP\u2010specific CD4<jats:sup>+<\/jats:sup> T cells causes spontaneous AIH\u2010like disease. T cell\u2010driven AIH in Alb\u2010iGP_Smarta mice was marked by autoantibodies and hepatic infiltration of plasma cells and B cells, particularly of isotype\u2010switched memory B cells, indicating antigen\u2010driven selection and activation. Immunosequencing of B cell receptor repertoires confirmed B cell expansion selectively in the liver, which was most likely driven by the hepatic GP model antigen, as indicated by branched networks of connected sequences and elevated levels of IgG antibodies to GP. However, intrahepatic B cells did not produce increased levels of cytokines and their depletion with anti\u2010CD20 antibody did not alter the CD4<jats:sup>+<\/jats:sup> T cell response in Alb\u2010iGP_Smarta mice. Moreover, B cell depletion did not prevent spontaneous liver inflammation and AIH\u2010like disease in Alb\u2010iGP_Smarta mice. In conclusion, selection and isotype\u2010switch of liver\u2010infiltrating B cells was dependent on the presence of CD4<jats:sup>+<\/jats:sup> T cells recognizing liver antigen. However, recognition of hepatic antigen by CD4<jats:sup>+<\/jats:sup> T cells and CD4<jats:sup>+<\/jats:sup> T cell\u2010mediated hepatitis was not dependent on B cells. Thus, autoreactive B cells can be bystanders and need not be drivers of liver inflammation in AIH.<\/jats:p>","DOI":"10.1111\/imm.13665","type":"journal-article","created":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T07:40:07Z","timestamp":1685173207000},"page":"214-229","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Autoantigen\u2010selected B cells are bystanders in spontaneous T cell\u2010driven experimental autoimmune hepatitis"],"prefix":"10.1111","volume":"170","author":[{"given":"David","family":"L\u00fcbbering","sequence":"first","affiliation":[{"name":"First Department of Medicine University Medical Centre Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Preti","sequence":"additional","affiliation":[{"name":"First Department of Medicine University Medical Centre Hamburg\u2010Eppendorf  Hamburg 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