Research ArticleImmunology

Diacylglycerol kinase ζ promotes actin cytoskeleton remodeling and mechanical forces at the B cell immune synapse

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Science Signaling  14 Apr 2020:
Vol. 13, Issue 627, eaaw8214
DOI: 10.1126/scisignal.aaw8214

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Balancing B cell signals

Diacylglycerol kinases (DGKs) catalyze the conversion of the lipid signaling molecule DAG into phosphatidic acid (PA), both of which have distinct effects. Merino-Cortés et al. found that the DGKζ isoform was critical in promoting signaling required for the optimal function of B cells. Compared with wild-type B cells, DGKζ-deficient B cells exhibited decreased mechanical forces at the plasma membrane, impairing the ability of these cells to form stable contacts with antigen-presenting cells, extract antigen, and present it to T cells. As a result, mice with DGKζ-deficient B cells showed diminished antibody responses in germinal centers. These data suggest that DGKζ regulates the balance in signaling between DAG and PA that is required for optimal B cell function.

Abstract

Diacylglycerol kinases (DGKs) limit antigen receptor signaling in immune cells by consuming the second messenger diacylglycerol (DAG) to generate phosphatidic acid (PA). Here, we showed that DGKζ promotes lymphocyte function–associated antigen 1 (LFA-1)–mediated adhesion and F-actin generation at the immune synapse of B cells with antigen-presenting cells (APCs), mostly in a PA-dependent manner. Measurement of single-cell mechanical force generation indicated that DGKζ-deficient B cells exerted lower forces at the immune synapse than did wild-type B cells. Nonmuscle myosin activation and translocation of the microtubule-organizing center (MTOC) to the immune synapse were also impaired in DGKζ-deficient B cells. These functional defects correlated with the decreased ability of B cells to present antigen and activate T cells in vitro. The in vivo germinal center response of DGKζ-deficient B cells was also reduced compared with that of wild-type B cells, indicating that loss of DGKζ in B cells impaired T cell help. Together, our data suggest that DGKζ shapes B cell responses by regulating actin remodeling, force generation, and antigen uptake–related events at the immune synapse. Hence, an appropriate balance in the amounts of DAG and PA is required for optimal B cell function.

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