Recombinant human CD40 ligand stimulates B cell proliferation and immunoglobulin E secretion

doi:10.1084/jem.176.6.1543

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Recombinant human CD40 ligand stimulates B cell proliferation and immunoglobulin E secretion

MK Spriggs, RJ Armitage, L Strockbine, KN Clifford, BM Macduff, TA Sato, CR Maliszewski and WC Fanslow
Department of Molecular Biology, Immunex Research and Development Corporation, Seattle, Washington 98101.

Signaling through the cell surface molecule, CD40, is known to play an important role in the proliferation and differentiation of B lymphocytes. Using the thymoma cell line EL4, we recently identified and cloned a cDNA encoding a murine ligand for the CD40 molecule (mCD40- L) and showed that it has biological activity in vitro. A cDNA encoding a human homologue of the mCD40-L was isolated using crosshybridization techniques from an activated peripheral blood T cell library. The predicted amino acid sequence indicates that this human ligand for CD40 (hCD40-L) is a 261 amino acid type II membrane protein that exhibits 78% amino acid identity with its murine counterpart. Northern blot and FACS analyses suggest that the hCD40-L is restricted in its expression to T lymphocytes, and that it is most abundant on the CD4+ T cell subpopulation. Cells transfected with hCD40-L caused the proliferation of human tonsil B cells in the absence of costimuli and, in the presence of interleukin 4, induced immunoglobulin E secretion from purified human B cells. A comparison of the efficacy of the hCD40-L and mCD40-L in these assays is presented.
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