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Expression of a V Region-Less B Cell Receptor Confers a Tolerance-Like Phenotype on Transgenic B Cells¹

Daniel Corcos^2,*, Alf Grandien, Aimé Vazquez, Olga Dunda^*, Patrick Lorès^* and Danielle Bucchini^*

^* Institut Cochin de Génétique Moléculaire, Institut National de la Santé et de la Recherche Médicale Unité 257, Paris, France; Department of Immunology, Wenner-Gren Institute, University of Stockholm, Stockholm, Sweden; and Institut National de la Santé et de la Recherche Médicale Unité 131, Clamart, France

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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