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Publication : Negative feedback regulation of antigen receptors through calmodulin inhibition of E2A.

First Author  Verma-Gaur J Year  2012
Journal  J Immunol Volume  188
Issue  12 Pages  6175-83
PubMed ID  22581853 Mgi Jnum  J:188878
Mgi Id  MGI:5442485 Doi  10.4049/jimmunol.1103105
Citation  Verma-Gaur J, et al. (2012) Negative feedback regulation of antigen receptors through calmodulin inhibition of E2A. J Immunol 188(12):6175-83
abstractText  Signaling from the BCR is used to judge Ag-binding strengths of the Abs of B cells. BCR signaling enables the selection for successive improvements in the Ag affinity over an extremely broad range of affinities during somatic hypermutation. We show that the mouse BCR is subject to general negative feedback regulation of the receptor proteins, as well as many coreceptors and proteins in signal pathways from the receptor. Thus, the BCR can downregulate itself, which can enable sensitive detection of successive improvements in the Ag affinity over a very large span of affinities. Furthermore, the feedback inhibition of the BCR signalosome and most of its proteins, as well as most other regulations of genes by BCR stimulation, is to a large extent through inhibition of the transcription factor E2A by Ca(2+)/calmodulin.
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