Protein Kinase C-β Dictates B Cell Fate by Regulating Mitochondrial Remodeling, Metabolic Reprogramming, and Heme Biosynthesis

Summary

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.

Graphical Abstract

Highlights

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  PKCβ in B cells promotes GC response and plasma cell differentiation in vivo

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  PKCβ regulates antigen polarization and antigen presentation in B cells

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  PKCβ drives mitochondrial remodeling and metabolic reprogramming in B cells

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  Metabolic reprogramming couples heme accumulation to instruct effector cell fate

Abstract

Lymphocyte activation is associated with major changes in metabolism. Tsui and colleagues demonstrate that PKCβ promotes metabolic reprogramming to drive effector fate decision in B cells.