NORMAL DEVELOPMENT BUT DIFFERENTIALLY ALTERED PROLIFERATIVE RESPONSESOF LYMPHOCYTES IN MICE LACKING CD81

CD81 (TAPA-1) is a member of the transmembrane 4 superfamily (TM4SF) w hich is expressed on the cell surface of most cells of the body throug hout their cellular differentiation. It has been recognized in several cell surface complexes of lymphocytes, suggesting that it may have di verse roles in lymphocyte development and activation regulation, Mice with a CD81 null mutation revealed normal T- and conventional B-cell d evelopment, although CD19 expression on B cells was dull and B-l cells were reduced in number, However, both T and B cells of mutant mice ex hibited strikingly enhanced proliferation in response to various types of stimuli. Interestingly, while proliferative responses of T cells f ollowing T-cell antigen receptor (TCR) engagement was enhanced in the absence of CD81, B-cell proliferation in response to B-cell antigen-re ceptor (BCR) cross-linking was severely impaired, Despite these altere d proliferative responses, both tyrosine phosphorylation and intracell ular calcium flux in response to cross-linking of cell surface antigen receptors were normal in mutant mice, reflecting apparently normal in itial signaling of antigen receptors, In conclusion, though CD81 is no t essential for normal T- and conventional B-cell development, it play s key roles in controlling lymphocyte homeostasis by regulating lympho cyte proliferation in distinct manners, dependent on the context of st imulation.