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

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

doi:10.1016/j.immuni.2018.04.031

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

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

Research output: Contribution to journal › Article › peer-review

88 Citations (Scopus)

264 Downloads (Pure)

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.

Original language	English
Journal	Immunity
Early online date	5 Jun 2018
DOIs	https://doi.org/10.1016/j.immuni.2018.04.031
Publication status	E-pub ahead of print - 5 Jun 2018

Keywords

B cells
BCR signaling
B cell activation
metabolic reprogramming

Access to Document

10.1016/j.immuni.2018.04.031Licence: CC BY

Protein Kinase C-β Dictates_TSUI_Accepted27April2018_GOLD VoR (CC BY)Final published version, 5.93 MBLicence: CC BY

Cite this

Tsui, C., Martinez-Martin, N., Gaya, M., Maldonado, P., Llorian, M., Legrave, N. M., Rossi, M., MacRae, J. I., Cameron, A. J., Parker, P. J., Leitges, M., Bruckbauer, A., & Batista, F. D. (2018). Protein Kinase C-β Dictates B Cell Fate by Regulating Mitochondrial Remodeling, Metabolic Reprogramming, and Heme Biosynthesis. Immunity. Advance online publication. https://doi.org/10.1016/j.immuni.2018.04.031

@article{86eea9d7b792404a8e4cf2b4bc257255,

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

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.",

keywords = "B cells, BCR signaling, B cell activation, metabolic reprogramming",

author = "Carlson Tsui and Nuria Martinez-Martin and Mauro Gaya and Paula Maldonado and Miriam Llorian and Legrave, {Nathalie M.} and Merja Rossi and MacRae, {James I.} and Cameron, {Angus J.} and Parker, {Peter J.} and Michael Leitges and Andreas Bruckbauer and Batista, {Facundo D.}",

year = "2018",

month = jun,

day = "5",

doi = "10.1016/j.immuni.2018.04.031",

language = "English",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

}

TY - JOUR

T1 - Protein Kinase C-β Dictates B Cell Fate by Regulating Mitochondrial Remodeling, Metabolic Reprogramming, and Heme Biosynthesis

AU - Tsui, Carlson

AU - Martinez-Martin, Nuria

AU - Gaya, Mauro

AU - Maldonado, Paula

AU - Llorian, Miriam

AU - Legrave, Nathalie M.

AU - Rossi, Merja

AU - MacRae, James I.

AU - Cameron, Angus J.

AU - Parker, Peter J.

AU - Leitges, Michael

AU - Bruckbauer, Andreas

AU - Batista, Facundo D.

PY - 2018/6/5

Y1 - 2018/6/5

N2 - 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.

AB - 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.

KW - B cells

KW - BCR signaling

KW - B cell activation

KW - metabolic reprogramming

U2 - 10.1016/j.immuni.2018.04.031

DO - 10.1016/j.immuni.2018.04.031

M3 - Article

SN - 1074-7613

JO - Immunity

JF - Immunity

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this