PKCβ-null (Prkcb^−/−) mice are severely immunodeficient. Here we show that mice whose B cells lack PKCβ failed to form germinal centers and plasma cells, which undermined affinity maturation and antibody production in response to immunization. Moreover, these mice failed to develop plasma cells in response to viral infection. At the cellular level, we have shown that Prkcb^−/− B cells exhibited defective antigen polarization and mTORC1 signaling. While altered antigen polarization impaired antigen presentation and likely restricted the potential of GC development, defective mTORC1 signaling impaired metabolic reprogramming, mitochondrial remodeling, and heme biosynthesis in these cells, which altogether overwhelmingly opposed plasma cell differentiation. Taken together, our study reveals mechanistic insights into the function of PKCβ as a key regulator of B cell polarity and metabolic reprogramming that instructs B cell fate.

PKCβ-null ( Prkcb ^-/- ) 小鼠存在严重的免疫缺陷。在这里，我们发现 B 细胞缺乏 PKCβ 的小鼠无法形成生发中心和浆细胞，这破坏了免疫反应中的亲和力成熟和抗体产生。此外，这些小鼠未能发育出应对病毒感染的浆细胞。在细胞水平上，我们发现Prkcb ^−/− B 细胞表现出抗原极化和 mTORC1 信号传导缺陷。虽然改变的抗原极化损害了抗原呈递并可能限制了GC发展的潜力，但有缺陷的mTORC1信号传导损害了这些细胞中的代谢重编程、线粒体重塑和血红素生物合成，这完全阻碍了浆细胞分化。总而言之，我们的研究揭示了 PKCβ 作为 B 细胞极性和指示 B 细胞命运的代谢重编程的关键调节因子的功能的机制。