Research ArticleImmunology

Diacylglycerol Kinase ζ Limits B Cell Antigen Receptor–Dependent Activation of ERK Signaling to Inhibit Early Antibody Responses

Science Signaling  15 Oct 2013:
Vol. 6, Issue 297, pp. ra91
DOI: 10.1126/scisignal.2004189

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Setting a Limit on Antibody Production

How much and what type of antibody a B cell produces depend on the strength and type of the stimulating signal. Engagement of the B cell antigen receptor (BCR) stimulates the phospholipase γ–dependent production of the second messenger diacylglycerol (DAG). In turn, DAG activates Ras–extracellular signal–regulated kinase (Ras-ERK) signaling, which is required for B cell proliferation and survival, as well as for their differentiation into antibody-secreting plasma cells. Wheeler et al. found that B cells deficient in the ζ isoform of DAG kinase (DGKζ), which phosphorylates DAG to attenuate its signaling, exhibited enhanced ERK activation and antibody production in vitro. Furthermore, mice deficient in DGKζ produced more antibodies than did wild-type mice in response to immunization with various antigens, suggesting that DGKζ limits BCR-dependent ERK signaling and antibody production.