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.
Kato
Ibuki
I
Department of Life Science, Tokyo Institute of Technology, Yokohama, Japan.
Sato
Hiromu
H
Kudo
Akira
A
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D019013:CD40 Antigens / Q000096:biosynthesis / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain / Q000187:drug effects; D006023:Glycoproteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D015851:Interleukin-7 / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction; D014162:Transfection
D019013:CD40 Antigens; D002352:Carrier Proteins; D006023:Glycoproteins; D007145:Immunoglobulin kappa-Chains; D015851:Interleukin-7; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse