The bone marrow microenvironment is critically important to the growth and maturation of normal human B cell precursors (BCP). The growth of human BCP in vivo or in vitro is dependent on the presence of bone marrow stromal cells expressing vascular cell adhesion molecule-1 (VCAM-1), to which BCP adhere via VLA-4 (integrin alpha4Beta1), and which probably produce growth-regulating cytokines. I propose to examine the signal transduction pathways initiated in bone marrow stromal cells following VCAM-1 dependent cell to cell adhesion. I also propose to examine the influence of signal transduction resulting from cell to cell adhesion on the production of the cytokines IL-7, IL-3 and TGF-Beta by human stromal cells.
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