The role of CD40-CD40 ligand interaction in human T cell-B cell collaboration.
Interactions between CD40 on B cells and its ligand on activated T cells have been reported to play an important role in T cell-B cell collaboration. In this current study, a mAb against the human CD40 ligand (5c8) was used to investigate the impact of CD40-CD40 ligand interactions in the initial activation of normal human peripheral blood B cells and in subsequent proliferation and differentiation. B cells were activated by co-culture with anti-CD3-stimulated normal T cells. mAb against CD40 ligand blocked initial T cell-dependent B cell activation, as assessed by [3H]uridine incorporation and IL-2R expression. Subsequent B cell proliferation and differentiation were also inhibited by this mAb. In addition to its effect on B cell activation, 5c8 also inhibited the capacity of B cells to augment IL-2 production by anti-CD3 activated T cells, implying a role for CD40-CD40 ligand interactions in the accessory function of B cells. Despite the importance of CD40-CD40 ligand interactions in T cell-B cell collaboration, CD40 ligand-deficient T cell clones were found to induce initial activation of B cells and support Ig production. This effect was only marginally effected by mAb to LFA-1 and ICAM-1, suggesting that additional interaction molecules play a role in T cell-B cell collaboration. Taken together, the data indicate that CD40-CD40 ligand interactions plays an important role in T cell-dependent B cell activation and subsequent differentiation but additional interaction structures are also involved in T cell-B cell collaboration.
Nishioka
Y
Y
Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center at Dallas 75235.
Lipsky
P E
PE
D000328:Adult; D000917:Antibody Formation; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens; D023201:CD40 Ligand; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008562:Membrane Glycoproteins / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D023201:CD40 Ligand