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Publication : The Ig-alpha ITAM is required for efficient differentiation but not proliferation of pre-B cells.

First Author  Storch B Year  2007
Journal  Eur J Immunol Volume  37
Issue  1 Pages  252-60
PubMed ID  17163454 Mgi Jnum  J:117076
Mgi Id  MGI:3695541 Doi  10.1002/eji.200636667
Citation  Storch B, et al. (2007) The Ig-alpha ITAM is required for efficient differentiation but not proliferation of pre-B cells. Eur J Immunol 37(1):252-260
abstractText  Signals from the pre-B cell receptor (pre-BCR) mediated by the cytoplasmic tails of Ig-alpha/Ig-beta are essential for developing B cells. To analyze the role of Ig-alpha ITAM and non-ITAM tyrosines in pre-BCR signaling, we reconstituted individual tyrosine mutants of Ig-alpha in src homology 2 domain-containing leukocyte protein of 65 kDa (SLP-65)/Ig-alpha double-deficient pre-B cells. We show that the Ig-alpha mutants led to comparable pre-BCR expression on the cell surface, while the pre-BCR-induced tyrosine phosphorylation was different. We further show that the reconstitution of Ig-alpha and the resulting pre-BCR expression led to enrichment of the pre-BCR-expressing cells in vitro irrespective of the introduced Ig-alpha mutation. We show that, even though the enrichment rate increased by lowering the IL-7 concentration, residual amounts of IL-7 were required for optimal enrichment. Our results indicate that surface IL-7 receptor expression is modulated by the pre-BCR, thereby increasing the IL-7 sensitivity of the respective cells. In contrast to the comparable pre-B cell proliferation, however, the Ig-alpha mutants differed in their capacity to induce calcium flux and activate efficient pre-B cell differentiation. Together, our data suggest that ITAM tyrosines and Y204 are required for efficient pre-B cell differentiation but not proliferation.Supporting information for this article is available at http://www.wiley-vch.de/contents/jc_2040/2007/36667_s.pdf.
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