Programmed cell death of B lymphocytes is induced by ligation of integrin-associated protein [CD47]

ABSTRACT

As part of the Immunoglobulin [Ig] superfamily, the transmembrane glycoprotein CD47 forms a signalling complex with the CD23 receptor alphavbeta3 integrin, which stimulates cytokine synthesis and controls inflammation by regulating leukocyte activation and the phagocytosis of aging apoptotic leukocytes. To investigate the effects of anti-CD47 antibodies on a range of cell types at varying stages of development. Using flow cytometric analysis, KMS11 and H929 human B lymphocyte multiple myeloma cell lines were used to study the expression of CD47 and alphavbeta3 integrin as a means to explore the factors relating to the induction and resistance to apoptosis. We found that both cell lines expressed high levels of CD47, with KMS11 cells expressing more than H929 cells. CD47 stimulated an increase in apoptosis in both KMS11 and H929 cells with the preponderance being late apoptotic, dying cells. Ligation of CD47 via the soluble phase was crucial for apoptosis to take place. These results provided an insight into the apoptotic mechanisms involved in the control of inflammation surrounding the activation and phagocytosis of leukocytes. In conclusion, further analysis is required to elucidate the complete signaling cascade responsible for this proliferative effect. Induction of apoptosis via CD47 stimulation appears to occur in the absence of CD47's signaling complex partner, alphavbeta3 whether or not apoptosis occurs, appears to be dependent upon the cell type and also the way CD47 is engaged