LYMPHOTOXIN-ALPHA IS AN IMPORTANT AUTOCRINE FACTOR FOR CD40-4-MEDIATED B-CELL ACTIVATION IN NORMAL AND ATOPIC DONORS(INTERLEUKIN)

Stimulation of human B cells with anti-CD40 + interleukin-4 (IL-4) res ults not only in proliferation and immunoglobulin E (IgE)-production, but also increased production of the cytokine lymphotoxin-alpha (LT-al pha) (formerly also known as tumour necrosis factor-beta (TNF-beta)). Here, we studied the role of LT-alpha (TNF-beta) in B cells following stimulation with anti-CD40 + IL-4 from normal versus atopic donors. An ti-CD40 + IL-4 stimulation of peripheral blood mononuclear cells (PBMC ) from atopic donors resulted in enhanced production of soluble LT-alp ha (TNF-beta) and increased membrane LT-alpha (TNF-beta) expression on the B cells compared with normal donors. Functional evaluation of LT- alpha (TNF-beta) in CD40 + IL-4-stimulated B cells shows that recombin ant LT-alpha (TNF-beta) induces proliferation of B cells and enhances CD40 + IL-4-mediated B-cell proliferation and IgE synthesis in both no rmal and atopic donors in a dose-dependent manner. These findings were supported by semiquantitative analysis of epsilon-germline transcript s using reverse transcription-polymerase chain reaction (RT-PCR) showi ng increased epsilon-germline transcription in the presence of LT-alph a. Furthermore, addition of anti-LT-alpha (anti-TNF-beta) to CD40 + IL -4-stimulated B cells partially inhibited proliferation and IgE synthe sis in a dose-dependent manner indicating a role of endogenous LT-alph a (TNF-beta) production by B cells during continued CD40 + IL-4 stimul ation. These data suggest that LT-alpha (TNF-beta) plays a potentially significant role during B-cell proliferation and IgE synthesis. Moreo ver, LT-alpha (TNF-beta) production seems to be differentially regulat ed in B cells from normal and atopic donors.