Abstract
TRANCE (TNF‐related activation‐induced cytokine)‐deficient mice completely lack osteoclasts, and develop severe osteopetrosis. These mice also show a defect in their pre‐B cell differentiation. In the present study, the expression of TRANCE was examined in pre‐B cell lines using flow cytometry and reverse transcription‐PCR. Three pre‐B cell lines, 18‐81, B~3~P~8~16‐1, and 38B9, expressed TRANCE on their surface, and two pre‐B cell lines, 70Z/3 and NFS5, at the late pre‐B cell stage, expressed it at low levels, although their mRNA expression was normal. Another pre‐B cell line, 38‐C‐13, at the intermediate stage between pre‐B and immature B cells, did not express TRANCE. The IL‐7‐dependent pre‐B cell line PreBR, which expresses the pre‐B cell receptor on the cellsurface, also expressed TRANCE. When differentiation of PreBR cells was induced in vitro by removing IL‐7 from cultures, TRANCE expression dropped; it was restored by the addition of IL‐7, suggesting that TRANCE functions in cooperation with IL‐7. To examine the function of TRANCE, we introduced the TRANCE gene into PreBR cells and established two transfectants that constitutively expressed TRANCE, even in the absence of IL‐7. In these transfectants, after removal of IL‐7, the number of cells that succeeded in κ chain rearrangement was decreased to one third; and CD40 expression decreased to less than one tenth. Moreover, the percentage of cells in the S/G2/M phase was increased by 50% over the mock transfectant. These findings indicate that, before κ chain rearrangement occurs, TRANCE together with IL‐7 induces pre‐B cells to proliferate and makes this rearrangement more efficient.