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

Academic Article

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 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.
  • Published In

  • Blood  Journal
  • Keywords

  • Antibody Diversity, B-Lymphocytes, Cell Differentiation, Clone Cells, Gene Expression Profiling, Gene Rearrangement, B-Lymphocyte, Humans, Immunoglobulin Fragments, Immunoglobulin Joining Region, Immunoglobulin Variable Region, Leukemia, B-Cell, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Tumor Cells, Cultured
  • Digital Object Identifier (doi)

    Author List

  • Wang Y-H; Zhang Z; Burrows PD; Kubagawa H; Bridges SL; Findley HW; Cooper MD
  • Start Page

  • 1030
  • End Page

  • 1037
  • Volume

  • 101
  • Issue

  • 3