SUPERANTIGENS INITIATE COGNATE CD4(-CELL B-CELL INTERACTIONS LEADING TO EARLY ACTIVATION AND PROLIFERATION OF B-CELLS() T)

Dimerization or even multimerization of various receptors is commonly required for signal transduction. We report here that clustering of ma jor histocompatibility complex class II molecules in human B cells by biotinylated staphylococcal enterotoxin A (SEA) cross-linked with avid in induces an increase in the level of intracellular calcium. This res ponse was abolished by prior treatment with protein tyrosine kinase (P TK) inhibitors, suggesting that SEA-triggered calcium mobilization in B cells is probably dependent on the activation of PTK. The implicatio n of PTK in SEA-induced early B cell activation was then confirmed by demonstrating that cross-linked SEA induces a significant increase in the level of tyrosine phosphorylation in B cells. The requirement of b iotin-avidin cross-linking in SEA-induced calcium mobilization in B ce lls can be fulfilled by the addition CD4(+) T cells, suggesting a role for CD4 molecules. Using the murine CD4(-) T cell hybridoma 3DT, or i ts derivative I1B3 transfected with human CD4 that both express SEA-sp ecific TCR, we confirmed the CD4 requirement for B cell calcium mobili zation and that both specific TCR and CD4 molecules are required in ea rly events of B cell activation induced by SEA. The role of CD4 in SEA -induced B cell proliferation was then investigated. SEA-stimulated B cells proliferated in the presence of CD4(+)T cells, whereas no respon se was observed in the presence of CD8(+) T cells. The addition of clo ne I1B3 CD4(+) T cells failed to fulfill the requirement of CD4(+) T c ells in SEA-induced B cell proliferation, indicating the possible invo lvement of other CD4(+) T cell surface molecules in this response. Thi s issue is currently under investigation.