title: Superantigens initiate cognate CD4+ T cell/B cell interactions leading to early activation and proliferation of B cells.
abstract: Dimerization or even multimerization of various receptors is commonly required for signal transduction. We report here that clustering of major histocompatibility complex class II molecules in human B cells by biotinylated staphylococcal enterotoxin A (SEA) cross-linked with avidin induces an increase in the level of intracellular calcium. This response was abolished by prior treatment with protein tyrosine kinase (PTK) inhibitors, suggesting that SEA-triggered calcium mobilization in B cells is probably dependent on the activation of PTK. The implication 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 biotinavidin cross-linking in SEA-induced calcium mobilization in B cells can be fulfilled by the addition CD4+ T cells, suggesting a role for CD4 molecules. Using the murine CD4- T cell hybridoma 3DT, or its derivative I1B3 transfected with human CD4 that both express SEA-specific TCR, we confirmed the CD4 requirement for B cell calcium mobilization and that both specific TCR and CD4 molecules are required in early 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 response was observed in the presence of CD8+ T cells. The addition of clone I1B3 CD4+ T cells failed to fulfill the requirement of CD4+ T cells in SEA-induced B cell proliferation, indicating the possible involvement of other CD4+ T cell surface molecules in this response. This issue is currently under investigation.
authors.affiliation: Centre de Recherche en Rhumatologie et Immunologie, Le Centre Hospitalier de l'Université Laval, Ste-Foy, Canada.
authors.forename: R
authors.initials: R
authors.lastname: al-Daccak
authors.forename: B
authors.initials: B
authors.lastname: Damaj
authors.forename: P H
authors.initials: PH
authors.lastname: Naccache
authors.forename: W
authors.initials: W
authors.lastname: Mourad
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D002460:Cell Line; D004768:Enterotoxins / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation / Q000276:immunology*; D011940:Receptor Aggregation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018089:Superantigens / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal