A defined metabolic state in pre B cells governs B-cell development and is counterbalanced by Swiprosin-2/EFhd1

Cell Death and Differentiation
Merle SteinDirk Mielenz

Abstract

B-cell development in the bone marrow comprises proliferative and resting phases in different niches. We asked whether B-cell metabolism relates to these changes. Compared to pro B and small pre B cells, large pre B cells revealed the highest glucose uptake and ROS but not mitochondrial mass, whereas small pre B cells exhibited the lowest mitochondrial membrane potential. Small pre B cells from Rag1-/-;33.C9 μ heavy chain knock-in mice revealed decreased glycolysis (ECAR) and mitochondrial spare capacity compared to pro B cells from Rag1-/- mice. We were interested in the step regulating this metabolic switch from pro to pre B cells and uncovered that Swiprosin-2/EFhd1, a Ca2+-binding protein of the inner mitochondrial membrane involved in Ca2+-induced mitoflashes, is expressed in pro B cells, but downregulated by surface pre B-cell receptor expression. Knockdown and knockout of EFhd1 in 38B9 pro B cells decreased the oxidative phosphorylation/glycolysis (OCR/ECAR) ratio by increasing glycolysis, glycolytic capacity and reserve. Prolonged expression of EFhd1 in EFhd1 transgenic mice beyond the pro B cell stage increased expression of the mitochondrial co-activator PGC-1α in primary pre B cells, but reduced mitochondrial ATP pro...Continue Reading

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Citations

Apr 25, 2018·Zeitschrift für Rheumatologie·G SchettR H Straub
Aug 1, 2018·International Journal of Molecular Sciences·Sophia UrbanczykDirk Mielenz
Jun 12, 2020·Cellular & Molecular Immunology·Jia-Huan XieJin Jin
May 18, 2020·Life Science Alliance·Valeria UlisseAvraham Yaron
Oct 22, 2019·European Journal of Immunology·Andrea CossarizzaArturo Zychlinsky
Feb 5, 2021·Frontiers in Cell and Developmental Biology·Sang A MunSoo Hyun Eom
Apr 1, 2021·Cellular & Molecular Immunology·Shree Padma Metur, Daniel J Klionsky
Jun 25, 2021·Frontiers in Immunology·Iwan G A Raza, Alexander J Clarke
Aug 8, 2021·International Journal of Molecular Sciences·Aikaterini Poulaki, Stavroula Giannouli
Dec 3, 2021·ELife·Drew WilfahrtVirginia Smith Shapiro

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