Research ArticleImmunology

The adaptor protein TRAF3 inhibits interleukin-6 receptor signaling in B cells to limit plasma cell development

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Science Signaling  01 Sep 2015:
Vol. 8, Issue 392, pp. ra88
DOI: 10.1126/scisignal.aaa5157

TRAF3 restrains plasma cells

Upon exposure to antigen, B cells differentiate to generate antibody-secreting cells called plasma cells. Multiple myeloma is an incurable malignancy characterized by the accumulation of abnormal numbers of plasma cells. Noting that mutations in the gene encoding the adaptor protein TRAF3 are associated with some cases of multiple myeloma, Lin et al. found that plasma cell numbers were increased in mice with a B cell–specific deficiency in TRAF3. Loss of TRAF3 in B cells resulted in increased responsiveness to the cytokine IL-6, which mediates the development and survival of plasma cells under normal conditions. In B cells from wild-type mice, TRAF3 associated with a phosphatase that targeted a transcription factor downstream of the IL-6 receptor, suggesting that TRAF3 limits the accumulation of plasma cells by inhibiting IL-6 signaling.

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