Mechanisms of T cell contact-dependent B cell activation.
It has been reported that activated Th cells express CD40 ligand, and the interaction of the CD40 ligand and CD40 on B cells results in B cell cycle entry. In this report, mechanisms of B cell activation induced by CD40-CD40 ligand interaction were studied by using an activated Th cell membrane as a source of CD40 ligand. The rise in cAMP concentration and tyrosine phosphorylation of a 69-kDa protein were induced in B cells stimulated with the activated Th cell membrane, and both of them were suppressed by the inclusion of soluble CD40 in cultures. The membrane stimulation did not elicit either inositol phosphates metabolism nor elevation of intracellular Ca2+ concentration. Protein kinase C depletion did not affect the proliferation, rise in cAMP level, or the 69-kDa protein tyrosine phosphorylation. Addition of anti-CD45 to the culture resulted in suppression of the B cell proliferation as well as the 69-kDa protein tyrosine phosphorylation. Furthermore, a protein kinase A inhibitor, H-89, suppressed the B cell proliferation induced by the membrane. These results indicate that both protein tyrosine kinase and protein kinase A were involved in the signal transduction pathway for the B cell proliferation evoked by the CD40-CD40 ligand interaction in Th cell contact-dependent B cell proliferation.
Kato
T
T
Department of Allergies, University of Tokyo, Japan.
Kokuho
T
T
Tamura
T
T
Nariuchi
H
H
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens; D002448:Cell Adhesion / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005260:Female; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation / Q000187:drug effects; D008211:Lymphocyte Cooperation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013449:Sulfonamides; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D007546:Isoquinolines; D010716:Phosphatidylinositols; D011506:Proteins; D013449:Sulfonamides; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D017493:Leukocyte Common Antigens; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide