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

Prior work has shown that parenterally administered anti-CD20 (5D2) inhibits CD4 T cell priming in response to challenge with and predisposes to pneumonia. In this study, we investigated the effect of subcutaneous anti-CD20 antibody and 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 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 infection, irrespective of primary or secondary infection. Anti-CD20 antibody therapy is used for both cancer and autoimmune disease but has been shown to be associated with pneumonia in humans. This study shows that low-dose subcutaneous anti-CD20 can modulate B cell populations without grossly perturbing fungal immunity against lung infection.