RT Journal Article
SR Electronic
T1 Immunoglobulin expression in the endoplasmic reticulum shapes the metabolic fitness of B lymphocytes
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000700
DO 10.26508/lsa.202000700
VO 3
IS 6
A1 Huda Jumaa
A1 Marieta Caganova
A1 Ellen J McAllister
A1 Laura Hoenig
A1 Xiaocui He
A1 Deniz Saltukoglu
A1 Kathrin Brenker
A1 Markus Köhler
A1 Ruth Leben
A1 Anja E Hauser
A1 Raluca Niesner
A1 Klaus Rajewsky
A1 Michael Reth
A1 Julia Jellusova
YR 2020
UL https://www.life-science-alliance.org/content/3/6/e202000700.abstract
AB 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.