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Immunoglobulin expression in the endoplasmic reticulum shapes the metabolic fitness of B lymphocytes

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Item Type:Article
Title:Immunoglobulin expression in the endoplasmic reticulum shapes the metabolic fitness of B lymphocytes
Creators Name:Jumaa, H. and Caganova, M. and McAllister, E.J. and Hoenig, L. and He, X. and Saltukoglu, D. and Brenker, K. and Köhler, M. and Leben, R. and Hauser, A.E. and Niesner, R. and Rajewsky, K. and Reth, M. and Jellusova, J.
Abstract:The major function of B lymphocytes is to sense antigens and to produce protective antibodies after activation. This function requires the expression of a B-cell antigen receptor (BCR), and evolutionary conserved mechanisms seem to exist that ensure that B cells without a BCR do not develop nor survive in the periphery. Here, we show that the loss of BCR expression on Burkitt lymphoma cells leads to decreased mitochondrial function and impaired metabolic flexibility. Strikingly, this phenotype does not result from the absence of a classical Syk-dependent BCR signal but rather from compromised ER expansion. We show that the reexpression of immunoglobulins (Ig) in the absence of the BCR signaling subunits Igα and Igβ rescues the observed metabolic defects. We demonstrate that immunoglobulin expression is needed to maintain ER homeostasis not only in lymphoma cells but also in resting B cells. Our study provides evidence that the expression of BCR components, which is sensed in the ER and shapes mitochondrial function, represents a novel mechanism of metabolic control in B cells.
Keywords:B-Cell Antigen Receptors, B-Lymphocytes, Burkitt Lymphoma, Endoplasmic Reticulum, Gene Knockout Techniques, Genetic Transduction, Homeostasis, Immunoglobulin M, Mitochondria, Phenotype, Signal Transduction, Syk Kinase, Transgenic Mice, Tumor Cell Line, Animals, Mice
Source:Life Science Alliance
Publisher:Life Science Alliance
Page Range:e202000700
Date:June 2020
Official Publication:https://doi.org/10.26508/lsa.202000700
PubMed:View item in PubMed

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