Effect of Subcutaneous Anti-CD20 Antibody-Mediated B Cell Depletion on Susceptibility to Pneumocystis Infection in Mice

Abstract

Prior work has shown that parenterally administered anti-CD20 (5D2) inhibits CD4⁺ T cell priming in response to challenge with Pneumocystis murina and predisposes to pneumonia. In this study, we investigated the effect of subcutaneous anti-CD20 antibody and Pneumocystis infection. In mice with primary infection, anti-CD20 antibody treatment depleted both CD19⁺ and CD27⁺ CD19⁺ cells but not T cells in the lung at days 14 and 28 after Pneumocystis inoculation. Although anti-CD20 antibody treatment impaired fungal clearance at day 14 postinfection, fungal burden in the lungs was substantially reduced at day 28 in both depleted and control mice in the low-dose group. Subcutaneous anti-CD20 antibody treatment did not alter antigen-specific serum immunoglobulin levels in mice compared with control mice, and there were no significant differences in the numbers of lung gamma interferon-positive (IFN-γ⁺) CD4⁺, interleukin 4-positive (IL-4⁺) CD4⁺, IL-5⁺ CD4⁺, and IL-17A⁺ CD4⁺ cells between depleted and control mice after infection. In mice with secondary infection, the lung fungal burden was comparable between depleted and control mice 14 days after reinfection. Low-dose subcutaneous anti-CD20 antibody treatment may delay fungal clearance, but it did not impair the ability of the host to clear Pneumocystis infection, irrespective of primary or secondary infection.IMPORTANCE Anti-CD20 antibody therapy is used for both cancer and autoimmune disease but has been shown to be associated with Pneumocystis pneumonia in humans. This study shows that low-dose subcutaneous anti-CD20 can modulate B cell populations without grossly perturbing fungal immunity against Pneumocystis lung infection.

Keywords: B cells; CD20; Pneumocystis.