IMMUNOGLOBULIN RECOMBINASE GENE ACTIVITY IS MODULATED RECIPROCALLY BYINTERLEUKIN-7 AND CD19 IN B-CELL PROGENITORS

Bone marrow stromal cells promote B cell development involving recombi nase gene-directed rearrangement of the immunoglobulin genes. We obser ved that the stromal cell-derived cytokine interleukin 7 (IL-7) enhanc es the expression of CD19 molecules on progenitor B-lineage cells in h uman bone marrow samples and downregulates the expression of terminal deoxynucleotidyl transferase (TdT) and the recombinase-activating gene s RAG-1 and RAG-2. Initiation of the TdT downregulation on the first d ay of treatment, CD19 upregulation during the second day, and RAG-1 an d RAG-2 downmodulation during the third day implied a cascade of IL-7 effects. While CD19 ligation by divalent antibodies had no direct effe ct on TdT or RAG gene expression, CD19 cross-linkage complete blocked the IL-7 downregulation of RAG expression without affecting the earlie r TdT response. These results suggest that signals rated through CD19 and the IL-7 receptor could modulate immunoglobulin gene rearrangement and repertoire diversification during the early stages of B cell diff erentiation.