V(D)J recombinatorial repertoire diversification during intraclonal pro-B to B-cell differentiation.
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 V(H) and V(L) 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.
Wang
Yui-Hsi
YH
Division of Developmental and Clinical Immunology, and Department of Medicine, University of Alabama at Birmingham and the Howard Hughes Medical Institute, Birmingham, AL 35294, USA.
Zhang
Zhixin
Z
Burrows
Peter D
PD
Kubagawa
Hiromi
H
Bridges
S Louis
SL
Findley
Harry W
HW
Cooper
Max D
MD
D000916:Antibody Diversity / Q000235:genetics*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D020869:Gene Expression Profiling; D015322:Gene Rearrangement, B-Lymphocyte; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics; D007133:Immunoglobulin Joining Region / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D015448:Leukemia, B-Cell / Q000276:immunology / Q000473:pathology; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000473:pathology; D014407:Tumor Cells, Cultured
D007128:Immunoglobulin Fragments; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region