ABSTRACT Background and Aims The hepatic inflammatory infiltrates in patients with primary biliary cholangitis (PBC) contain variable numbers of B cells and plasma cells; however, their potential as therapeutic targets remains uncertain. This study aims to investigate the pathological characteristics and therapeutic implications of plasma cells and B cells in PBC. Methods We collected liver tissue from 55 PBC patients, alongside serological data from the time of sampling and 1 year following ursodeoxycholic acid (UDCA) treatment. To evaluate the effects of plasma cell and B cell depletion, we utilised dnTGF‐βRII mice treated with bortezomib and anti‐CD20 monoclonal antibody, respectively. Additionally, we performed an adoptive transfer of plasma cells from dnTGF‐βRII mice into C57BL/6J mice to investigate their pathogenicity. Results In PBC patients, hepatic infiltration of plasma cells and B cells was correlated strongly with liver inflammation and fibrosis, disease staging, and titers of PBC‐related autoantibodies. The number of plasma cells (but not B cells) was also higher in UDCA non‐responders than in responders. Notably, plasma cells depletion in dnTGF‐βRII mice alleviated portal inflammation and reduced levels of AMA, IgM and IgG. Furthermore, the adoptive transfer of plasma cells from dnTGF‐βRII mice into DDC‐fed C57BL/6J mice resulted in AMA production, exacerbated cholestasis, and worsened fibrosis. In contrast, B cell depletion did not alleviate portal inflammation or fibrosis in dnTGF‐βRII mice. Conclusions The data indicate a pathogenic role for plasma cells in PBC. The depletion of plasma cells alleviated cholangitis in PBC mice, indicating a promising new therapeutic strategy for PBC.
Zhang et al. (Thu,) studied this question.