T-CELL-DEPENDENT INDUCTION OF NF-KAPPA-B IN B-CELLS

In comparison to B cell stimulation mediated by surface immunoglobulin (Ig) antigen receptor ligation, little is known about the intracellular events associated with T cell-dependent B cell responses. A model for the efferent phase of T cell-B cell interaction was used to examine the capacity of activated T cells to trigger nuclear expression of the trans-acting transcription factor, NF-kappaB, in B cells. Fixed, activated, but not fixed, resting Th2 cells were found to induce increased binding activity for a kappaB site-containing oligonucleotide in a time-dependent manner. This induction of NF-kappaB was eliminated by an antibody directed against a 39-kD cell interaction protein on activated T cells as well as by a soluble form of B cell CD40. Of particular relevance to intracellular signaling, NF-kappaB induction was not diminished by prior depletion of B cell protein kinase C (PKC) with phorbol myristate acetate. These results strongly suggest that T cell-dependent B cell stimulation is associated with NF-kappaB induction via p39-CD40 interaction and that this is brought about by non-PKC dependent signaling, in marked contrast to the previously documented requirement for PKC in sIg receptor-mediated stimulation. This suggests that NF-kappaB responds to more than one receptor-mediated intracellular signaling pathway in B cells and may be part of a ''final common pathway'' for B cell stimulation.