Targeted inactivation of the tetraspanin CD37 impairs T-cell-dependent B-cell response under suboptimal costimulatory conditions

CD37 is a membrane protein of the tetraspanin superfamily, which includes C D9, CD53, CD63, CD81, and CD82, Many of these molecules are expressed on le ukocytes and have been implicated in signal transduction, cell cell interac tions, and cellular activation and development, We generated and analyzed m ice deficient for CD37. Despite the high expression of CD37 on cells of the immune system, no changes in development and cellular composition of lymph oid organs were observed in mice lacking CD37, Analyses of humoral immune r esponses revealed a reduced level of immunoglobulin G1 (IgG1) in the sera o f nonimmunized mice and an alteration of responses to T-cell-dependent anti gens, Antibody responses to model antigen administered in the absence of ad juvant and to viral infections were generally poor in CD37-deficient mice. These poor antibody responses could be overcome by the immunization of anti gen together with adjuvant, These results suggest a role for CD37 in T-cell -B-cell interactions which manifests itself under suboptimal costimulatory conditions.