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Publication : Expression of a V region-less B cell receptor confers a tolerance-like phenotype on transgenic B cells.

First Author  Corcos D Year  2001
Journal  J Immunol Volume  166
Issue  5 Pages  3083-9
PubMed ID  11207259 Mgi Jnum  J:133777
Mgi Id  MGI:3784132 Doi  10.4049/jimmunol.166.5.3083
Citation  Corcos D, et al. (2001) Expression of a V region-less B cell receptor confers a tolerance-like phenotype on transgenic B cells. J Immunol 166(5):3083-9
abstractText  Neoplastic B cells from H chain disease patients express a truncated B cell receptor (BCR), comprising a membrane Ig that lacks part of its extracellular domain. It has been speculated that deletion of the Ag binding domain would confer a constitutive activity on the BCR, as it has been shown for oncogenic growth factor receptors. A V region-less BCR has constitutive activity, because in transgenic mice it causes inhibition of endogenous H chain gene rearrangements and relieves the requirement for surrogate L chain in pre-B cell development. However, it has been speculated that normal Ag receptors also display constitutive activity. Here we show that transgenic B cells expressing a membrane H chain disease protein on their surface are phenotypically and functionally similar to B cells developing in the presence of their cognate Ag and that cells with normal levels of mutant BCR are eliminated in spleen via a bcl-2 sensitive pathway while progressing toward the mature stage. In contrast, cells with lower levels of mutant receptors develop as mature B cells. These findings support the view that the truncated BCR has a constitutive activity that mimics ligand binding, in analogy to what has been shown for oncogenic growth factor receptors.
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