stimulation of protein tyrosine phosphorylation in human b cells after ligation of the beta 1 integrin vla4 b lymphocytes express several adhesion molecules that are involved in cellcell and cellextracellular matrix interactions the alpha 4 beta 1 integrin vla4 expressed on preb and matureactivated b cells mediates adhesion of these cells to its two ligands vcam1 and fibronectin recent evidence suggests that vla4 is involved in t lymphocyte activation however relatively little is known of the role of vla4 in b cell differentiation to begin to assess the potential involvement of vla4 in b cell activation we have examined the effect of ligation of vla4 on protein tyrosine phosphorylation in b cells we found that crosslinking of vla4 by either mab or natural ligands ie vcam1 and the fn40 cleavage fragment of fibronectin induced the tyrosine phosphorylation of a 110kda protein in a human preb cell line nalm6 an ebvtransformed b cell line sb and normal tonsillar b cells these findings suggest that vla4 can activate a tyrosine kinase in b cells and b cell lines these signals may be involved in the subsequent differentiation of preb and mature b cells within specific microenvironments where vla4 mediated adhesion is operational