BCL6b mediates the enhanced magnitude of the secondary response of memory CD8 T lymphocytes

Abstract

A characteristic of the secondary response of CD8 T cells that distinguishes it from the primary response is the generation of greater numbers of effector cells. Because effector CD8 T cells are derived from a pool of less differentiated, replicating cells in secondary lymphoid organs, and because IL-2 mediates effector differentiation, the enhanced secondary response may reflect the enlargement of this generative pool by the transient repression of IL-2-mediated differentiation. We have examined for this function the transcriptional represser BCL6b, a homologue of BCL6 that represses IL-2-induced B cell differentiation. BCL6b is expressed in a small subset of antigen-experienced CD8 T cells. Ectopic expression of BCL6b in CD8 T cells diminishes their growth in response to IL-2 in vitro. Female mice in which the BCL6b gene has been interrupted have normal primary responses of CD8 T cells to infection with vaccinia expressing the H-Y epitope, Uty, but Uty-specific, BCL6b , memory CD8 T cells have diminished recall proliferative responses to this epitope in vitro. BCL6b mice also have normal primary CD8 T cell responses to influenza infection, but nucleoprotein peptide-specific, BCL6b , memory CD8 T cells have a cell autonomous defect in the number of effector cells generated in response to reinfection. Therefore, BCL6b is required for the enhanced magnitude of the secondary response of memory CD8 T cells