Department of Biology, Boston College, 140 Commonwealth Avenue, 414 Higgins Hall, Chestnut Hill, MA 02467, USA.
Biochem J. 2012 Nov 15;448(1):165-9. doi: 10.1042/BJ20121225.
Signals derived from the BCR (B-cell antigen receptor) control survival, development and antigenic responses. One mechanism by which BCR signals may mediate these responses is by regulating cell metabolism. Indeed, the bioenergetic demands of naïve B-cells increase following BCR engagement and are characterized by a metabolic switch to aerobic glycolysis; however, the signalling pathways involved in this metabolic reprogramming are poorly defined. The PKC (protein kinase C) family plays an integral role in B-cell survival and antigenic responses. Using pharmacological inhibition and mice deficient in PKCβ, we demonstrate an essential role of PKCβ in BCR-induced glycolysis in B-cells. In contrast, mice deficient in PKCδ exhibit glycolytic rates comparable with those of wild-type B-cells following BCR cross-linking. The induction of several glycolytic genes following BCR engagement is impaired in PKCβ-deficient B-cells. Moreover, blocking glycolysis results in decreased survival of B-cells despite BCR engagement. The results establish a definitive role for PKCβ in the metabolic switch to glycolysis following BCR engagement of naïve B-cells.
BCR（B 细胞抗原受体）信号控制着 B 细胞的存活、发育和抗原应答。BCR 信号可能通过调节细胞代谢来介导这些反应的一种机制。事实上，在 BCR 结合后，幼稚 B 细胞的生物能量需求增加，并表现出向有氧糖酵解的代谢转变；然而，参与这种代谢重编程的信号通路尚未明确。PKC（蛋白激酶 C）家族在 B 细胞存活和抗原应答中发挥着重要作用。我们通过药理学抑制和 PKCβ 缺陷小鼠证明，PKCβ 在 BCR 诱导的 B 细胞糖酵解中起着重要作用。相比之下，在 BCR 交联后，PKCδ 缺陷小鼠的糖酵解率与野生型 B 细胞相当。BCR 结合后，PKCβ 缺陷 B 细胞中几种糖酵解基因的诱导受到损害。此外，尽管 BCR 结合，但阻断糖酵解会导致 B 细胞存活率下降。这些结果确立了 PKCβ 在幼稚 B 细胞 BCR 结合后向糖酵解代谢转变中的明确作用。
