Proceedings of the National Academy of Sciences · 1992 · 810 citations · 25 references
Life SciencesImmunologyMolecular BiologyCellular ImmunologyMonoclonal AntibodiesSignal TransductionB Cell ActivationB Cell BiologyHumoral ImmunityLymphocyte ActivationT Cell ActivationT Cell BiologyCd40 Signaling In B CellsCell ActivationCell Growth RegulationMonoclonal Antibody SpecificityT Helper Cells
CD40 is a B‑cell surface receptor that promotes B‑cell growth when cross‑linked by antibodies. The study identifies a 39‑kDa protein on activated helper T cells as the CD40 ligand required for Th‑dependent B‑cell activation, and shows that blocking this interaction inhibits B‑cell proliferation and differentiation.
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.
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