B cell CD19 is transferred between immune cells in mice and humans

Abstract

Abstract When immune cells interact, they frequently exchange membrane-bound antigens. Our evolving understanding of these processes challenges the cellular specificity of lineage markers and therapeutic monoclonal antibodies. By using mouse and human B-T cell co-cultures, we report that CD19, an assumingly exclusive B cell marker, is transferred via trogocytosis when B cells activate T cells. In a B cell-driven model of experimental autoimmune encephalomyelitis, CD19 + T cells expand and show enhanced features of activation, differentiation, and encephalitogenic potential ex vivo. Additionally, co-transfer of CD19 and functional IgM from B cells results in the gain of B cell function by T cells. In patients with chronic central nervous system (CNS) demyelination, CD19 + T cells display a pro-inflammatory phenotype and are concomitantly depleted by inebilizumab, an approved anti-CD19 antibody, which raises important considerations for the therapeutic use of monoclonal antibodies overall. Finally, we report that myeloid cells acquire CD19 and functional IgM after phagocytosis of apoptotic B cells and thereby gain functional B cell properties. These findings highlight the commonness of membrane and antigen-transfer between cells, resulting in transmission of cellular function.