BACKGROUND AND OBJECTIVES: An increased level of serum M-protein IgG may affect the growth or survival of myeloma cells through the Fcgamma inverted exclamation mark receptor (FcgammaR) in human myelomas. We examined the expression of FcgammaR (CD32, CD16 and CD64) and compared the effect of anti-CD32 antibody on the viability of myeloma cells to that on the viability of normal plasma cells. DESIGN AND METHODS: Surface antigen and gene expressions were examined by flow cytometry and reverse transcription polymerase chain reaction, respectively. We examined the effect of anti-CD32 antibody on the viability of CD19- myeloma cells (including immature and mature myeloma cells) and CD19+ normal plasma cells. In order to confirm the involvement of CD19 in the anti-CD32-mediated growth suppression, we used CD19 transfectants of myeloma, B-cell and erythroleukemia cell lines that we have already established. RESULTS: CD32 was significantly expressed on primary myeloma cells, but immature, MPC-1- myeloma cells expressed CD32 more weakly than mature, MPC-1+ cells. Treatment with anti-CD32 antibody decreased the viability of normal plasma cells (CD38++ CD19+) more than that of myeloma cells (CD38++ CD19-); CD32-mediated growth suppression was greater in mature MPC-1+ cells than in immature MPC-1- cells. The introduction of CD19 into CD19- cell lines significantly increased the sensitivity of the cells to treatment with anti-CD32 antibody as well as addition of IgG complex; furthermore, increased phosphorylation of CD32 and SHIP was detected in CD19-transfected cell lines. INTERPRETATION AND CONCLUSIONS: Myeloma cells lacking CD19 expression are less sensitive to CD32-mediated growth suppression than are CD19+ normal plasma cells.
BACKGROUND AND OBJECTIVES: An increased level of serum M-protein IgG may affect the growth or survival of myeloma cells through the Fcgamma inverted exclamation mark receptor (FcgammaR) in humanmyelomas. We examined the expression of FcgammaR (CD32, CD16 and CD64) and compared the effect of anti-CD32 antibody on the viability of myeloma cells to that on the viability of normal plasma cells. DESIGN AND METHODS: Surface antigen and gene expressions were examined by flow cytometry and reverse transcription polymerase chain reaction, respectively. We examined the effect of anti-CD32 antibody on the viability of CD19- myeloma cells (including immature and mature myeloma cells) and CD19+ normal plasma cells. In order to confirm the involvement of CD19 in the anti-CD32-mediated growth suppression, we used CD19 transfectants of myeloma, B-cell and erythroleukemia cell lines that we have already established. RESULTS:CD32 was significantly expressed on primary myeloma cells, but immature, MPC-1- myeloma cells expressed CD32 more weakly than mature, MPC-1+ cells. Treatment with anti-CD32 antibody decreased the viability of normal plasma cells (CD38++ CD19+) more than that of myeloma cells (CD38++ CD19-); CD32-mediated growth suppression was greater in mature MPC-1+ cells than in immature MPC-1- cells. The introduction of CD19 into CD19- cell lines significantly increased the sensitivity of the cells to treatment with anti-CD32 antibody as well as addition of IgG complex; furthermore, increased phosphorylation of CD32 and SHIP was detected in CD19-transfected cell lines. INTERPRETATION AND CONCLUSIONS:Myeloma cells lacking CD19 expression are less sensitive to CD32-mediated growth suppression than are CD19+ normal plasma cells.
Authors: Ping Zhou; Raymond L Comenzo; Adam B Olshen; Ezio Bonvini; Scott Koenig; Peter G Maslak; Martin Fleisher; James Hoffman; Suresh Jhanwar; James W Young; Stephen D Nimer; Adam M Boruchov Journal: Blood Date: 2008-01-23 Impact factor: 22.113