Impact of B-cell depletion therapy on respiratory viral infection

Abstract

Abstract B cell depletion therapy with anti-CD20 antibodies ameliorates autoimmune diseases such as multiple sclerosis, rheumatoid arthritis as well as haematological malignancies. Anti-CD20 antibodies deplete pre-B cells, mature B cells and malignant B cells but do not reduce plasma cells. Recently, studies have associated anti-CD20 therapy with severe manifestation of SARS-CoV2 infection. However, the mechanism of this adverse effect of anti-CD20 therapy remains unclear. This study was undertaken to investigate the effect of anti-CD20 therapy on respiratory viral infection. C57BL/6 mice were treated with anti-CD20 antibody to induce B cell depletion and then were infected intratracheally with H1N1 Influenza A mouse-adapted A/Puerto Rico/8/1934 virus (IAV). Our results show that B cell depletion therapy worsens lung infection with more severe and prolonged weight loss. Higher viral titers were found in the lungs of anti-CD20 treated mice, indicating impairment in virus clearance. Flow cytometry analysis showed no difference between groups in CD4+ and CD8+ PR8 antigen specific T cells on day 9 post-infection. However, higher numbers of inflammatory, SiglecF+ neutrophils were found in B cell depleted mice. In summary, our data show that anti-CD20 therapy exacerbates the viral pathology in respiratory lung infections. We further have identified that B cell depletion therapy affects viral clearance and inflammatory neutrophils but has no effect on T cell numbers in the lung at the peak of infection. Our future studies will identify the mechanisms driving the severe pathology in influenza infection with B cell depletion. Supported by grants from NIH (R01AI137047 and R01EY027346) A grant awarded to Dr. Kovatz and Dr Axtell from the Presbyterian Health Foundation