PD1+CD4+ T cells promote receptor editing and suppress autoreactivity of CD19+CD21low B cells within the lower respiratory airways in adenovirus pneumonia

Abstract

Human adenovirus (HAdV) pneumonia poses a major health burden for young children, however, factors that contribute to disease severity remain elusive. We analyzed immune cells from bronchoalveolar lavage (BAL) of children with HAdV pneumonia and found that CD19⁺CD21^low B cells were significantly enriched in the BAL and were associated with increased autoantibody concentrations and disease severity. Myeloid cells, PD-1⁺CD4⁺ T helper cells and CD21^low B cells formed tertiary lymphoid structures within the respiratory tracts. Myeloid cells promoted autoantibody production by expressing high amounts of B cell activating factor (BAFF). In contrast, PD-1⁺CD4⁺ T helper cells induced production of IgG1 and IgG3 antibodies but suppressed autoreactive IgGs by initiating B cell receptor editing. In summary, this study reveals cellular components involved in protective versus autoreactive immune pathways in the respiratory tract, and these findings provide potential therapeutic targets for severe HAdV lower respiratory tract infections.