Ligation of B7 with CD28/CTLA-4 on T cells results in CD40 ligand expression, interleukin-4 secretion and efficient help for antibody production by B cells.
It has been extensively shown that when T cells are co-stimulated with B7-CD28 interaction, a strong proliferative as well as cytolytic T cell response can be induced. In contrast, there exists only indirect evidence that the B7-CD28 interaction is of importance for the induction of T cell helper functions in B cell responses. Here we have used mouse fibroblasts transfected with the human Fc gamma receptor type II and human B7 to address this issue. We found that T cells, when activated through the T cell receptor (TcR)/CD3 complex with monoclonal antibodies and co-stimulated by B7-CD28 interaction, can provide efficient help for the induction of both IgM and IgG production by resting B cells. This helper activity is, at least in part, mediated by the interaction between the CD40 ligand on the T cells and CD40 on the B cells. We also demonstrate that more than one signal to the T cell is required for the induction of the CD40 ligand, one being delivered through the TcR/CD3 complex and the second by ligation of CD28 with the B7 molecule. In addition to the induction of cognate T helper function, we provide evidence that co-stimulation of T cells with B7-CD28 interaction can result in the secretion of both Th1- and Th2-type lymphokines.
de Boer
M
M
Department of Immunology, Innogenetics, N.V., Belgium.
Kasran
A
A
Kwekkeboom
J
J
Walter
H
H
Vandenberghe
P
P
Ceuppens
J L
JL
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000502:physiology*; D018122:B7-1 Antigen / Q000502:physiology*; D018106:CD28 Antigens / Q000502:physiology*; D017252:CD3 Complex / Q000502:physiology; D023201:CD40 Ligand; D002460:Cell Line; D002648:Child; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D008875:Middle Aged; D013601:T-Lymphocytes / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D015847:Interleukin-4