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

Neoplastic B cells from H chain disease patients express a truncated B cell receptor (BCR), comprising a membrane Ig that lacks part of its extracellu lar domain. It has been speculated that deletion of the Ag binding domain w ould confer a constitutive activity on the BCR, as it has been shown for on cogenic growth factor receptors. A V region-less BCR has constitutive activ ity, because in transgenic mice it causes inhibition of endogenous H chain gene rearrangements and relieves the requirement for surrogate L chain in p re-B cell development. However, it has been speculated that normal Ag recep tors also display constitutive activity. Here we show that transgenic B cel ls expressing a membrane H chain disease protein on their surface are pheno typically and functionally similar to B cells developing in the presence of their cognate Ag and that cells with normal levels of mutant BCR are elimi nated in spleen via a bcl-2 sensitive pathway while progressing toward the mature stage. In contrast, cells with lower levels of mutant receptors deve lop as mature B cells. These findings support the view that the truncated B CR has a constitutive activity that mimics ligand binding, in analogy to wh at has been shown for oncogenic growth factor receptors.