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Prepublished online as a Blood First Edition Paper on September 19, 2002; DOI 10.1182/blood-2002-06-1828.
Submitted June 24, 2002
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA * Corresponding author; email: Max.Cooper{at}ccc.uab.edu.
The initial B cell repertoire is generated by combinatorial immunoglobulin V(D)J gene segment rearrangements that occur in a preferential sequence. Because cellular proliferation occurs during the course of these rearrangement events, it has been proposed that intraclonal diversification occurs during this phase of B cell development. An opportunity to directly examine this hypothesis was provided by the identification of a human acute lymphoblastic leukemic cell line that undergoes spontaneous differentiation from pro-B cell to the pre-B and B cell stages with concomitant changes in the gene expression profile that normally occur during B cell differentiation. After confirming the clonality of the progressively differentiating cells, an analysis of Ig genes and transcripts indicated that pro-B cell members marked by the same DJ rearrangement generated daughter B cells with multiple VH and VL gene segment rearrangements. These findings validate the principle of intraclonal V(D)J diversification during B cell generation and define a manipulable model of human B cell differentiation.
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