ALPHA-4-BETA-7 INTEGRIN MEDIATES B-CELL BINDING TO FIBRONECTIN AND VASCULAR CELL-ADHESION MOLECULE-1 - EXPRESSION AND FUNCTION OF ALPHA-4 INTEGRINS ON HUMAN B-LYMPHOCYTES

Cell-cell and cell-extracellular matrix interactions are mediated by a wide array of cell surface molecules known as adhesion receptors, inc luding the integrin family that comprises numerous alphabeta heterodim ers. A new integrin group, the beta7 subfamily, has been recently defi ned. Its two members, alpha4beta7 and alpha(H)beta7, are involved in t he lymphocyte migration to the Peyer's patches and the intestinal muco sa, respectively. We have analyzed the expression of alpha4beta7 integ rin on B cells from different cellular compartments and at different a ctivation states. Resting peripheral blood B lymphocytes constitutivel y express large amounts of alpha4beta7. By contrast, alpha4beta7 integ rin, which is absent on resident B cells from different lymphoid tissu es, is induced upon activation. Functional studies indicates that alph a4beta7 is mediating B cell attachment to fibronectin and vascular cel l adhesion molecule-1 through distinct epitopes on this integrin. Furt hermore, the alpha4beta7 integrin is also implicated in intercellular interactions as deduced by the ability of anti-alpha4beta7 mAb to trig ger homotypic B cell aggregation. Finally, alpha4beta7 and alpha4beta1 integrins redistribute at the cell membrane in a similar clustering p attern when B cells attach to fibronectin- and vascular cell adhesion molecule-1-coated surfaces. Our studies demonstrate the differential r egulation on the expression and function of alpha4beta7 integrin among different human B cell populations.