A 39-kDa protein on activated helper T cells binds CD40 and transduces the signal for cognate activation of B cells.
CD40 is a B-cell surface molecule that has been shown to induce B-cell growth upon ligation with monoclonal antibodies. This report shows that triggering via CD40 is essential for the activation of resting B cells by helper T cells (Th). A soluble fusion protein of CD40 and human immunoglobulin, CD40-Ig, inhibited the induction of B-cell cycle entry, proliferation, and differentiation by activated Th1 and Th2. The ligand for CD40 was identified as a 39-kDa membrane protein that was selectively expressed on activated Th. A monoclonal antibody specific for the 39-kDa protein inhibited CD40-Ig binding and also inhibited the activation of B cells by Th. These data indicate that the 39-kDa membrane protein expressed on activated Th is a binding protein for CD40 and functions to transduce the signal for Th-dependent B-cell activation.
Noelle
R J
RJ
Department of Micribiology, Dartmouth Medical School, Lebanon, NH 03756.
Roy
M
M
Shepherd
D M
DM
Stamenkovic
I
I
Ledbetter
J A
JA
Aruffo
A
A
D000818:Animals; D000911:Antibodies, Monoclonal; D000917:Antibody Formation; D015703:Antigens, CD / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D000954:Antigens, Surface / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019013:CD40 Antigens; D002453:Cell Cycle; D002454:Cell Differentiation; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008811:Mice, Inbred DBA; D011485:Protein Binding; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D019013:CD40 Antigens; D008565:Membrane Proteins