Cytokines play critical roles in regulating the proliferation, differentiation, and survival of hematopoietic and lymphoid cells. In order to study the cytokine regulation in early B cell development, we developed a long-term bone marrow lymphoid culture system that selectively generates pre-pro-B cells and pro-B cells. Using this system, we have purified a heterodimer containing IL-7 and HGFb , which is responsible for the generation of these primitive lymphoid precursors. We have cloned and expressed the IL-7/HGFb as a single chain molecule connected by a flexible linker in different expression systems. rIL-7/HGFb was found to bind to and to signal through both the IL-7 and c-met receptors. Studies are in progress to 1) further characterize the receptor complex for IL-7/HGFb; 2) further study the functions of IL-7/HGFb on early B cells, hematopoietic stem cells, embryonic stem cells in vitro and in vivo; and 3) determine the signal transduction pathways activated by IL-7/HGFb .

Lai L, Zeff RA, and Goldschneider I. A recombinant single-chain IL-7/HGFb hybrid cytokine induces juxtacrine interactions of the IL-7 and HGF (c-met) receptors and stimulates the proliferation of CFU-S12, common lymphoid progenitors (CLP) and pre-pro-B cells. Blood 107:1776-1784.

Wei C, Lai L, and Goldschneider I. (2002) Pre-pro-B cell growth-stimulating factor (PPBSF) upregulates IL-7R alpha chain expression and enables pro-B cells to respond to monomeric IL-7. J Interferon Cytokine Res. 22:823-832.

Lai L and Goldschneider I. (2001) Cutting edge: Identification of a hybrid cytokine consisting of IL-7 and the beta-chain of the hepatocyte growth factor/scatter factor. J Immunol. 167:3550-3554.

Lai L, Chen F, McKenna S, and Goldschneider I. (1998) Identification of an IL-7-associated pre-pro-B cell growth-stimulating factor (PPBSF). II. PPBSF is a covalently linked heterodimer of IL-7 and a Mr 30,000 cofactor. J Immunol. 160:2280-2286.

McKenna SD, Chen F, Lai L, and Goldschneider I. (1998) Identification of an IL-7-associated pre-pro-B cell growth-stimulating factor (PPBSF). I. Production of the non-IL-7 component by bone marrow stromal cells from IL-7 gene-deleted mice. J Immunol. 160:2272-2279.