TRANCE together with IL-7 induces pre-B cells to proliferate

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, B3P816-1, and 38B9, expressed TRANCE on their surface, and two pre-B cell lines, 7OZ/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 cell surface, 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 kappa 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 kappa chain rearrangement occurs, TRANCE together with IL-7 induces pre-B cells to proliferate and makes this rearrangement more efficient.