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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. and Schwarzer, R. and Calkhoven, C.F. and Kaufman, R. and Doerken, B. and 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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