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

Beitrag in einer Fachzeitschrift
(Originalarbeit)


Details zur Publikation

Autor(en): Stein M, Dütting S, Mougiakakos D, Boesl MR, Fritsch K, Reimer D, Urbanczyk S, Steinmetz T, Schuh W, Bozec A, Winkler T, Jäck HM, Mielenz D
Zeitschrift: Cell Death and Differentiation
Verlag: Nature Publishing Group
Jahr der Veröffentlichung: 2017
ISSN: 1476-5403


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 Ca-binding protein of the inner mitochondrial membrane involved in Ca-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 production at the pro to pre B cell transition in IL-7 cultures. Transgenic EFhd1 expression caused a B-cell intrinsic developmental disadvantage for pro and pre B cells. Hence, coordinated expression of EFhd1 in pro B cells and by the pre BCR regulates metabolic changes and pro/pre B-cell development.Cell Death and Differentiation advance online publication, 19 May 2017; doi:10.1038/cdd.2017.52.



FAU-Autoren / FAU-Herausgeber

Bozec, Aline Prof. Dr.
Juniorprofessur für Osteoimmunologie
Jäck, Hans-Martin Prof. Dr.
Professur für Immunologie
Mielenz, Dirk PD Dr.
Medizinische Fakultät
Mougiakakos, Dimitrios
Professur für Hämatologie/Onkologie mit dem Schwerpunkt Tumorimmunologie
Reimer, Dorothea
Lehrstuhl für Genetik
Stein, Merle
Professur für Immunologie
Steinmetz, Tobit
Professur für Immunologie
Urbanczyk, Sophia
Molekular-Immunologische Abteilung in der Medizinischen Klinik 3
Winkler, Thomas Prof. Dr.
Professur für Genetik


Autor(en) der externen Einrichtung(en)
Universitätsklinikum Würzburg


Zitierweisen

APA:
Stein, M., Dütting, S., Mougiakakos, D., Boesl, M.R., Fritsch, K., Reimer, D.,... Mielenz, D. (2017). A defined metabolic state in pre B cells governs B-cell development and is counterbalanced by Swiprosin-2/EFhd1. Cell Death and Differentiation. https://dx.doi.org/10.1038/cdd.2017.52

MLA:
Stein, Merle, et al. "A defined metabolic state in pre B cells governs B-cell development and is counterbalanced by Swiprosin-2/EFhd1." Cell Death and Differentiation (2017).

BibTeX: 

Zuletzt aktualisiert 2018-08-08 um 13:24