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

TitleProtein Kinase C-β Dictates B Cell Fate by Regulating Mitochondrial Remodeling, Metabolic Reprogramming, and Heme Biosynthesis.
Publication TypeJournal Article
Year of Publication2018
AuthorsTsui C, Martinez-Martin N, Gaya M, Maldonado P, Llorian M, Legrave NM, Rossi M, MacRae JI, Cameron AJ, Parker PJ, Leitges M, Bruckbauer A, Batista FD
JournalImmunity
Volume48
Issue6
Pagination1144-1159.e5
Date Published06/19/2018
ISSN1097-4180
Abstract

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.

DOI10.1016/j.immuni.2018.04.031
Alternate JournalImmunity
PubMed ID29884460
PubMed Central IDPMC6015119
Grant List / / Wellcome Trust / United Kingdom
UM1 AI100663 / AI / NIAID NIH HHS / United States
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