Immunoglobulin recombinase gene activity is modulated reciprocally by interleukin 7 and CD19 in B cell progenitors.
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.
Billips
L G
LG
Department of Medicine, University of Alabama at Birmingham 35294, USA.
Nuñez
C A
CA
Bertrand
F E
FE
Stankovic
A K
AK
Gartland
G L
GL
Burrows
P D
PD
Cooper
M D
MD
D018941:Antigens, CD19 / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects*; D001483:Base Sequence; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D004253:DNA Nucleotidylexotransferase / Q000096:biosynthesis; D004254:DNA Nucleotidyltransferases / Q000235:genetics*; D004268:DNA-Binding Proteins; D015536:Down-Regulation / Q000187:drug effects; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D018398:Homeodomain Proteins; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D014176:Protein Biosynthesis; D015854:Up-Regulation / Q000187:drug effects; D045567:VDJ Recombinases
D018941:Antigens, CD19; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D015851:Interleukin-7; D009687:Nuclear Proteins; C499311:RAG2 protein, human; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases; D004253:DNA Nucleotidylexotransferase