Title
Regulation of B cell Development by Antigen Receptors: Studies on the physiological roles of E2A transcription factors and their,Used
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The Eprotein E2A is well known for its many roles during B cell development. Antigen receptor signaling that leads to inhibition of E2A by the calciumsensor protein calmodulin (CaM) has therefore very broad implications. The down regulation of the surrogate light chains of the preB cell receptor and also the coreceptor CD19 was shown to be through CaM inhibition of E2A. Furthermore, several components of the Ig recombination machinery including RAG1 and RAG2 are downregulated by this mechanism, and the recombination complex was shown to include the RAGs, Pax5 and E2A, which can be directly released from the Ig heavy chain locus by preB cell receptor signaling through CaM to achieve allelic exclusion. The tight regulation of the antibody diversification enzyme AID is also dependent on CaM inhibition of E2A, and a negative feedback regulation of the preB and B cell receptor proteins and coreceptors and proteins in signal pathways from the receptor was also shown to occur through E2A inhibition by CaM. Plasma cell differentiation is induced by very fast regulatory events, which are shown to be dependent on CaM inhibition of E2A.
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