A small molecule Abl kinase inhibitor induces differentiation of Abelson virus–transformed pre-B cell lines
- 2 December 2002
- journal article
- research article
- Published by Springer Nature in Nature Immunology
- Vol. 4 (1) , 31-37
Abstract
Abelson murine leukemia virus–transformed cell lines have provided a critical model system for studying the regulation of B cell development. However, transformation by v-Abl blocks B cell development, resulting in the arrest of these transformants in an early pre-B cell–like state. We report here that treatment of Abelson virus–transformed pre-B cell lines with the small molecule Abl kinase inhibitor (STI571) results in their differentiation to a late pre-B cell–like state characterized by induction of immunoglobulin (Ig) light chain gene rearrangement. DNA microarray analyses enabled us to identify two genes inhibited by v-Abl that encode the Igk 3′ enhancer–binding transcription factors Spi-B and IRF-4. We show that enforced expression of these two factors is sufficient to induce germline Igk transcription in Abelson-transformed pro-B cell lines. This suggests a key role for these factors, and perhaps for c-Abl itself, in the regulated activation of Ig light chain gene rearrangement.Keywords
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