Abl-mediated transformation, immunoglobulin gene rearrangements and arrest of B lymphocyte differentiation.

The abl oncogene was originally discovered in Abelson virus, a murine retrovirus. This virus and the protein tyrosine kinase encoded by abl are well known for their ability to transform B lymphocyte progenitors. Most of the transformed cells resemble a normal B lineage progenitor called a pre-B cell and appear to be arrested in differentiation at the stage of immunoglobulin light chain gene rearrangement. Recent evidence obtained using temperature-sensitive Abelson virus mutants provides direct support for this idea. Lymphoid cells transformed by one such virus undergo light chain rearrangement soon after shift to the nonpermissive temperature. This event is accompanied by several changes classically associated with light chain gene rearrangement including increased activity of the NF-kappa B transcription factor, expression of light chain RNAs and increased levels of expression of the RAG-1 and RAG-2 genes. Although the mechanism by which abl protein blocks the activity of these factors is not yet known, these data suggest that tyrosine phosphorylation may be intimately connected to regulation of early B cell development and expression of genes that are central to all phases of antigen receptor gene rearrangement.