Eukaryotic initiation factor 2α phosphorylation is required for B cell maturation and function in mice

Mielke, N.; Schwarzer, R.; Calkhoven, C.F.; Kaufman, R.; Doerken, B.; Leutz, A.; Jundt, F.

Eukaryotic initiation factor 2α phosphorylation is required for B cell maturation and function in mice

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Item Type:	Article
Title:	Eukaryotic initiation factor 2α phosphorylation is required for B cell maturation and function in mice
Creators Name:	Mielke, N., Schwarzer, R., Calkhoven, C.F., Kaufman, R., Doerken, B., Leutz, A. and Jundt, F.
Abstract:	Background. The control of translation initiation is a crucial component in the regulation of gene expression. The eukaryotic initiation factor 2{alpha}(eIF2{alpha}) mediates binding of the initiator tmRNA to the AUG initiation codon, and thus controls a rate-limiting step in translation initiation. Phosphorylation of eIF2{alpha} at serine 51 (S51) is linked to cellular stress response and attenuates translation initiation. The biochemistry of translation inhibition mediated by eIF2{alpha} phosphorylation is well characterized, yet the physiological importance in hematopoiesis remains only partially known. Design and Methods. Using hematopoietic stem cells carrying a non-phosphorylatable S51A mutant form of eIF2{alpha} (eIF2{alpha}AA), we examined the efficiency of reconstitution in wildtype (WT) or B cell-deficient microMT({mu}MT) C57BL/6 recipients in two independent models. Results. We provide evidence that phosphorylation-deficient S51A eIF2{alpha} mutant hematopoietic stem cells may repopulate lethally irradiated mice but have a defect in the development and maintenance of newly formed B cells in the bone marrow and of naïve follicular B (FOB) cells in the periphery. The mature B cell compartment is markedly reduced in bone marrow, spleen and peripheral blood, and B cell receptor (BCR)-mediated proliferation in vitro and serum immunoglobulin (Ig) secretion in vivo are impaired. Conclusions. The data suggest that regulation of translation through eIF2{alpha} phosphorylation is dispensable in hematopoietic reconstitution but essential during late B cell development.
Keywords:	Hematopoiesis, Lymphocytes, B Cell Development, eIF2&{alpha} Phosphorylation, Translation Initiation, Animals, Mice
Source:	Haematologica
ISSN:	0390-6078
Publisher:	European Hematology Association
Volume:	96
Number:	9
Page Range:	1261-1268
Date:	September 2011
Official Publication:	https://doi.org/10.3324/haematol.2011.042853
PubMed:	View item in PubMed

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