Integrin-associated protein/CD47 regulates motile activity in human B-cell lines through CDC42

Cell migration requires a dynamic interaction between the cell, its substrate, and the cytoskeleton-associated motile apparatus. Integrin-associated protein (IAP)/ CD47 is a 50-kd cell surface protein that is physically associated with beta 3 integrins and that modulates the functions of beta 3 integrins in various cells. However, in B-lymphocytes that express beta 1 integrins but few beta 3 integrins, the roles of IAP/ CD47 remain to be determined. Cross-linking of IAP/CD47 by the immobilized anti-IAP/CD47 monoclonal antibody (mAb) B6H12, but not 2D3, produced signals to promote polarization with lamellipodia, a characteristic morphology during leukocyte migration, in pre-B and mature B-cell lines (BALL, Nalm6, ONHL-1, Daudi), but not in myeloma cell lines (RPM18226, OPM-2). In the presence of the immobilized fibronectin (FN), soluble B6H12 could increase the rate of the polarization and activate migratory activity of BALL cells to FN in a transwell filter assay. Furthermore, the dominant-negative form of CDC42 completely blocked B6H12-induced morphologic and functional changes without inhibiting phorbol 12-myristate 13-acetate-induced spreading on FN in BALL cells, whereas the dominant-negative form of Rac1 inhibited all these changes. These findings demonstrate that in B lymphocytes, IAP/CD47 may transduce the signals to activate the migratory activity, in which CDC42 may be specifically involved, end that IAP/ CD47 shows synergistic effect with alpha 4 beta 1 on B cell migration. These findings would provide new insight into the role of IAP/CD47 on B-cell function. (Blood. 2000; 96:234-241) (C) 2000 by The American Society of Hematology.