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

Publication date: Available online 5 June 2018
Source:Immunity
Author(s): Carlson Tsui, Nuria Martinez-Martin, Mauro Gaya, Paula Maldonado, Miriam Llorian, Nathalie M. Legrave, Merja Rossi, James I. MacRae, Angus J. Cameron, Peter J. Parker, Michael Leitges, Andreas Bruckbauer, Facundo D. Batista
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.

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Teaser

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.


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