REGULATION OF HUMAN B-CELL FUNCTION BY RECOMBINANT CD40 LIGAND AND OTHER TNF-RELATED LIGANDS

To assess the potential of CD40 ligand (CD40L) and the related molecul es CD27 ligand (CD27L), CD30 ligand (CD30L), and membrane TNF-alpha to stimulate B cell responses, expression of these proteins in the bacul ovirus system was performed. Sf9 cells expressing these membrane molec ules were cultured with normal human B cells and a variety of B cell l ines to assess the functional outcome. The signal provided by CD40L pr omotes aggregation of B cells, stimulates vigorous proliferation, and induces germ-line transcription of downstream heavy chain constant reg ion genes in the absence of cytokine costimulation. In contrast, CD27L , CD30L, and TNF-alpha had no effects on B cell proliferation. CD27L a nd TNF-alpha had no effect on the induction of germ-line transcripts, whereas CD30L consistently inhibited constitutive and CD40L-induced ge rm-line transcription of the epsilon gene by B cell lines that express CD30. These results demonstrate that various members of the TNF famil y exert specific effects on human B cell function, with CD40L and CD30 L providing powerful, but opposing, effects on I epsilon transcription .