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

doi:10.1084/jem.182.4.973

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

LG Billips, CA Nunez, FE Bertrand 3rd, AK Stankovic, GL Gartland, PD Burrows and MD Cooper
Department of Medicine, University of Alabama at Birmingham 35294, USA.

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.
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