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B, IL-6, and IgE in Human B Lymphocytes1
Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206
Stimulation of human peripheral B cells via the CD40 receptor and
IL-4R together lead to IgE synthesis and secretion, but the
intracellular signaling mechanisms by which these signals lead to IgE
production are unclear. Roles for the transcription factor NF-
B and
IL-6 have been postulated in the induction of IgE synthesis by
IL-4/CD40. We found that neither anti-CD40 Ab nor IL-4 alone was
able to induce significant proliferation of human B cells. However, the
combination of anti-CD40 and IL-4 was a potent inducer of B cell
proliferation in addition to IgE production from purified human B
cells. Furthermore, IL-4 and anti-CD40 synergized for the
production of IL-6. While neither IL-4 alone nor anti-CD40 alone
was able to induce significant NF-B DNA binding activity, the
combination of IL-4 and anti-CD40 induced a strong activation of
NF-B, a transcription factor that regulates IL-6 production. These
data indicate that both IL-4 and anti-CD40 are required to induce
NF-B activation and IL-6 transcription and production, and implicate
these events in a signaling pathway augmenting IgE production in human
B lymphocytes.
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