Lymphotoxin‐α is an important autocrine factor for CD40+interleukin‐4‐mediated B‐cell activation in normal and atopic donors

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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-α (LT-α) (formerly also known as tumour necrosis factor-β (TNF-β)). Here, we studied the role of LT-α (TNF-β) 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-α (TNF-β) and increased membrane LT-α (TNF-β) expression on the B cells compared with normal donors. Functional evaluation of LT-α (TNF-β) in CD40+IL-4-stimulated B cells shows that recombinant LT-α (TNF-β) 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 ε-germline transcripts using reverse transcription–polymerase chain reaction (RT–PCR) showing increased ε-germline transcription in the presence of LT-α. Furthermore, addition of anti-LT-α (anti-TNF-β) to CD40+IL-4-stimulated B cells partially inhibited proliferation and IgE synthesis in a dose-dependent manner indicating a role of endogenous LT-α (TNF-β) production by B cells during continued CD40+IL-4 stimulation. These data suggest that LT-α (TNF-β) plays a potentially significant role during B-cell proliferation and IgE synthesis. Moreover, LT-α (TNF-β) production seems to be differentially regulated in B cells from normal and atopic donors.