PMID- 12184921 OWN - NLM STAT- MEDLINE DCOM- 20030211 LR - 20181130 IS - 1079-9907 (Print) IS - 1079-9907 (Linking) VI - 22 IP - 7 DP - 2002 Jul TI - Pre-pro-B cell growth-stimulating factor (PPBSF) upregulates IL-7Ralpha chain expression and enables pro-B cells to respond to monomeric IL-7. PG - 823-32 AB - Although pro-B cells are well represented in IL-7 knockout (KO) mice, they express abnormally low concentrations of the interleukin-7 receptor alpha-chain (IL-7Ralpha) and do not generate pre-B cells. Here, we demonstrate that pro-B cells from IL-7 KO mice can be induced to generate pre-B cells and immature B cells by exposure to recombinant IL-7 (rIL-7) in vivo but not in vitro. Experiments in recombinant activation gene-1 (RAG-1) KO mice indicate that the in vitro unresponsiveness of IL-7(-/-) pro-B cells to rIL-7 is unrelated to the absence of a functional pre-B cell receptor (pre-BCR). Rather, it appears to be due to the suboptimal expression of the IL-7Ralpha chain. Thus, IL-7(-/-) pro-B cells readily respond to rIL-7 in vitro if IL-7Ralpha chain expression is first upregulated by exposure to IL-7 in vivo or to IL-7(+/+) bone marrow (BM) stromal cells or conditioned medium (CM) therefrom in vitro. Similar results were obtained when pro-B cells from IL-7 KO mice were cultured on IL-7(-/-) BM stromal cells in the presence of rIL-7. This suggested that the recently described pre-pro-B cell growth-stimulating factor (PPBSF), a self-assembling hybrid cytokine comprising IL-7 and the stromal cell-derived hepatocyte growth factor beta-chain (HGFbeta), is required to stimulate pro-B cells from IL-7 KO mice. This inference was verified by demonstrating that purified PPBSF upregulates IL-7Ralpha chain expression on IL-7(-/-) pro-B cells in vitro and enables them to respond to rIL-7 in a stepwise manner. We, therefore, postulate that PPBSF is the operative form of IL-7 that normally induces IL-7Ralpha(lo) pre-pro-B cells to proliferate and differentiate into IL-7Ralpha(hi) pro-B cells, which then proliferate and differentiate into pre-B cells on stimulation with monomeric IL-7. FAU - Wei, Chiju AU - Wei C AD - Department of Pathology, School of Medicine, University of Connecticut Health Center, Farmington, CT 06030-3105, USA. FAU - Lai, Laijun AU - Lai L FAU - Goldschneider, Irving AU - Goldschneider I LA - eng GR - AI32752/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Interferon Cytokine Res JT - Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research JID - 9507088 RN - 0 (Chemokine CXCL12) RN - 0 (Chemokines, CXC) RN - 0 (Culture Media, Conditioned) RN - 0 (Cxcl12 protein, mouse) RN - 0 (Interleukin-7) RN - 0 (Protein Subunits) RN - 0 (Receptors, Interleukin-7) RN - 0 (Recombinant Proteins) RN - 0 (interleukin-7 receptor, alpha chain) RN - 67256-21-7 (Hepatocyte Growth Factor) SB - IM MH - Animals MH - B-Lymphocyte Subsets/cytology MH - Bone Marrow MH - Cell Differentiation/drug effects MH - Cell Division/drug effects MH - Cell Lineage MH - Chemokine CXCL12 MH - Chemokines, CXC/chemistry/*pharmacology MH - Culture Media, Conditioned/pharmacology MH - Dimerization MH - Female MH - Genes, RAG-1 MH - Hepatocyte Growth Factor/chemistry MH - Interleukin-7/*pharmacology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Protein Subunits MH - Receptors, Interleukin-7/*biosynthesis/genetics MH - Recombinant Proteins/pharmacology MH - Stromal Cells/cytology/metabolism MH - Up-Regulation/drug effects EDAT- 2002/08/20 10:00 MHDA- 2003/02/13 04:00 CRDT- 2002/08/20 10:00 PHST- 2002/08/20 10:00 [pubmed] PHST- 2003/02/13 04:00 [medline] PHST- 2002/08/20 10:00 [entrez] AID - 10.1089/107999002320271422 [doi] PST - ppublish SO - J Interferon Cytokine Res. 2002 Jul;22(7):823-32. doi: 10.1089/107999002320271422.