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Prepublished online as a Blood First Edition Paper on September 19, 2002; DOI 10.1182/blood-2002-06-1828.

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Blood, 1 February 2003, Vol. 101, No. 3, pp. 1030-1037

IMMUNOBIOLOGY

V(D)J recombinatorial repertoire diversification during intraclonal pro-B to B-cell differentiation

Yui-Hsi Wang, Zhixin Zhang, Peter D. Burrows, Hiromi Kubagawa, S. Louis Bridges Jr, Harry W. Findley, and Max D. Cooper

From the Division of Developmental and Clinical Immunology, and Departments of Medicine, Pediatrics, Pathology, and Microbiology, University of Alabama at Birmingham and the Howard Hughes Medical Institute, Birmingham, AL; and Division of Pediatric Hematology/Oncology/Bone Marrow Transplantation, Emory University School of Medicine, Atlanta, GA.

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 examine this hypothesis directly 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 immunoglobulin 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.

© 2003 by The American Society of Hematology.
 

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