BCL6b Mediates the Enhanced Magnitude of the Secondary Response of Memory CD8+ T Lymphocytes

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 repressor 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, BCL6 b-/-, memory CD8+ T cells have diminished recall proliferative responses to this epitope in vitro. BCL6 b-/- mice also have normal primary CD8+ T cell responses to influenza infection, but nucleoprotein peptide-specific, BCL6 b-/-, 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.