The Depletion of Plasma Cells but Not CD20+B Cells Alleviates Primary Biliary Cholangitis.

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.