GENE-TARGETED B-DEFICIENT MICE REVEAL A CRITICAL ROLE FOR B-CELLS IN THE CD4 T-CELL RESPONSE

The role of a cells in promoting T cell responses is still controversial. In this study, we use JHD mice which have a targeted mutation in the J(H) gene and are thus rendered deficient in a cells to address this issue. We show here that immunization of JHD mice with soluble antigen falls to prime CD4 T cells, for either clonal expansion or delivery of immunological help for antibody responses. This lack of CD4 T cell priming in JHD mice corresponds to a 3- to g-fold lower co-stimulatory activity of antigen-presenting cells (APC) from the JHD mice, as measured by anti-CD3-induced proliferative responses of CD4 T cells. This in turn is due to a defect of APC from JHD mice in response to T cell-mediated induction of co-stimulatory activity. As the development of macrophages and dendritic cells is unaffected in the JHD mice, our results demonstrate that B cells play a critical role in CD4 T cell priming, possibly by delivering a critical co-stimulatory activity for clonal expansion of CD4 T cells.