A critical role for DRAK2 in the germinal center reaction and the antibody response (84.1)

Abstract

Abstract DRAK2 (DAP-related apoptotic kinase-2) protein is a DAP family member. DRAK2 is highly expressed in B and T lymphocytes and it is among the few proteins that are highly enriched in the lymphoid system. To determine whether DRAK2 plays a role in B cell activation and differentiation, we analyzed the germinal center development in the spleen of drak2−/− mice immunized with a T cell-dependent (TD) antigen. Immunofluorescence microscopy and FACS analysis showed the number of germinal centers was three to five-folds less in the drak2−/− mice than in their wild type littermates. Impairment of germinal center development was not due to a deficiency in B cell proliferation, as BrdU uptake in vivo and CFSE staining ex vivo of B cells was comparable in DRAK2-deficient and wild type B cells. 7-AAD and TUNEL staining experiments showed that, the proportion of apoptotic germinal center B and T cells in drak2−/− mice was significantly higher than wild type mice. As a result, the generation of high affinity IgG antibodies was impaired in drak2−/− mice. Specific expression of bcl-xl in T cells of drak2−/− mice rescued germinal center formation. Thus, our findings suggest a novel role of DRAK2 in the germinal center reaction and the maturation of the antibody response. Supported by N.I.H. grants AR 40908, AI 45011 and AI 60573.