X-linked lymphoproliferative disease (XLP) is a human disease characterized by hypogammaglobulinemia that results from mutations in a gene encoding SLAM-associated protein (SAP), which facilitates signaling in T cells. Although CD4 T cell responses are intact in SAP-deficient (SAP-) mice, SAP is required in CD4 T cells for normal plasma cell responses against viral infection, suggesting that a critical B cell helper function of CD4 T cells is missing when CD4 T cells lack SAP. However, when or in what form this helper function is delivered is unknown. We hypothesize that CD4 T cells can migrate into B cell follicles but cannot deliver SAP-dependent survival signals to B cells early in the immune response such that the B cells die by apoptosis. To test this hypothesis, we will determine when during an immune response SAP is required by reconstituting SAP- mice with wild type CD4 T cells at different times (aim I). We will then compare migration of SAP and wild type CD4 T cells during the immune response (aim II). Finally, we will identify the fate of B cells and plasma cells in SAP- mice by determining whether there is altered apoptosis, proliferation, or differentiation of these cells (aim III), which will suggest potential CD4 T cell defects to further analyze. ? ?
|Kamperschroer, Cris; Roberts, Deborah M; Zhang, Yongqing et al. (2008) SAP enables T cells to help B cells by a mechanism distinct from Th cell programming or CD40 ligand regulation. J Immunol 181:3994-4003|
|Kamperschroer, Cris; Dibble, John P; Meents, Dana L et al. (2006) SAP is required for Th cell function and for immunity to influenza. J Immunol 177:5317-27|