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, Harry W. Findley, Max D. Cooper

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1030-1037
Number of pages8
JournalBlood
Volume101
Issue number3
DOIs
Publication statusPublished - Feb 1 2003

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Wang, Y. H., Zhang, Z., Burrows, P. D., Kubagawa, H., Bridges, S. L., Findley, H. W., & Cooper, M. D. (2003). V(D)J recombinatorial repertoire diversification during intraclonal pro-B to B-cell differentiation. Blood, 101(3), 1030-1037. https://doi.org/10.1182/blood-2002-06-1828