Lymphotoxin-alpha is an important autocrine factor for CD40 + interleukin-4-mediated B-cell activation in normal and atopic donors (original) (raw)

Abstract

Stimulation of human B cells with anti-CD40 + interleukin-4 (IL-4) results not only in proliferation and immunoglobulin E (IgE)-production, but also increased production of the cytokine lymphotoxin-alpha (LT-alpha) (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. Anti-CD40 + IL-4 stimulation of peripheral blood mononuclear cells (PBMC) from atopic donors resulted in enhanced production of soluble LT-alpha (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 recombinant LT-alpha (TNF-beta) induces proliferation of B cells and enhances CD40 + IL-4-mediated B-cell proliferation and IgE synthesis in both normal and atopic donors in a dose-dependent manner. These findings were supported by semiquantitative analysis of epsilon-germline transcripts using reverse transcription-polymerase chain reaction (RT-PCR) showing increased epsilon-germline transcription in the presence of LT-alpha. Furthermore, addition of anti-LT-alpha (anti-TNF-beta) to CD40 + IL-4-stimulated B cells partially inhibited proliferation and IgE synthesis in a dose-dependent manner indicating a role of endogenous LT-alpha (TNF-beta) production by B cells during continued CD40 + IL-4 stimulation. These data suggest that LT-alpha (TNF-beta) plays a potentially significant role during B-cell proliferation and IgE synthesis. Moreover, LT-alpha (TNF-beta) production seems to be differentially regulated in B cells from normal and atopic donors.

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Selected References

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