Immunoglobulin recombinase gene activity is modulated reciprocally by interleukin 7 and CD19 in B cell progenitors.

Academic Article

Abstract

  • Bone marrow stromal cells promote B cell development involving recombinase gene-directed rearrangement of the immunoglobulin genes. We observed that the stromal cell-derived cytokine interleukin 7 (IL-7) enhances the expression of CD19 molecules on progenitor B-lineage cells in human bone marrow samples and downregulates the expression of terminal deoxynucleotidyl transferase (TdT) and the recombinase-activating genes RAG-1 and RAG-2. Initiation of the TdT downregulation on the first day of treatment, CD19 upregulation during the second day, and RAG-1 and RAG-2 downmodulation during the third day implied a cascade of IL-7 effects. While CD19 ligation by divalent antibodies had no direct effect on TdT or RAG gene expression, CD19 cross-linkage complete blocked the IL-7 downregulation of RAG expression without affecting the earlier TdT response. These results suggest that signals generated through CD19 and the IL-7 receptor could modulate immunoglobulin gene rearrangement and repertoire diversification during the early stages of B cell differentiation.
  • Published In

    Keywords

  • Antigens, CD19, B-Lymphocytes, Base Sequence, Bone Marrow Cells, Cell Differentiation, Cell Survival, Cells, Cultured, DNA Nucleotidylexotransferase, DNA Nucleotidyltransferases, DNA-Binding Proteins, Down-Regulation, Flow Cytometry, Gene Expression Regulation, Hematopoietic Stem Cells, Homeodomain Proteins, Humans, Interleukin-7, Molecular Sequence Data, Nuclear Proteins, Protein Biosynthesis, Up-Regulation, VDJ Recombinases
  • Author List

  • Billips LG; Nuñez CA; Bertrand FE; Stankovic AK; Gartland GL; Burrows PD; Cooper MD
  • Start Page

  • 973
  • End Page

  • 982
  • Volume

  • 182
  • Issue

  • 4