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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.
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