Malignant plasma cell lines express a functional CD28 molecule.
The function of CD28 molecules that are present on malignant plasma cells of human myeloma cell lines (HMCL) was studied. First, myeloma cells expressed a similar density of CD28 antigen to that of normal T cells. The myeloma CD28 molecules were able to bind B7-Ig molecules as well as L cells transfected with a B7-1 cDNA, and anti-CD28 mAb inhibited the binding. Myeloma cells did not express B7-1 antigens but a low density of B7-2 antigens. The myeloma B7-2 molecules of two HMCL were able to bind CTLA-4 protein. No autocrine CD28:B7-2 activation could be evidenced as we found no spontaneous binding of the p85 subunit of PI-3 kinase to CD28 molecules. In addition, a blocking anti-CD28 mAb did not affect the IL-6-dependent or autonomous proliferation of the HMCL. The activation of myeloma CD28 molecules with or without TPA stimulation did not affect the proliferation, survival, differentiation, expression of activation antigens and cytokine receptors or cytokine production of myeloma cells. However, the triggering of myeloma CD28 molecules by B7-1 transfectant cells resulted in binding of the p85 subunit of PI-3 kinase to CD28 molecules as previously shown for T cell CD28 molecules. This expression of a large density of CD28 molecules able to bind B7 molecules might contribute to a downregulation of the immune control of myeloma cells.
Zhang
X G
XG
Institute of Molecular Genetics, Unit for Cellular Therapy, Hôpital Saint Eloi, Montpellier, France.
Olive
D
D
Devos
J
J
Rebouissou
C
C
Ghiotto-Ragueneau
M
M
Ferlin
M
M
Klein
B
B
D018122:B7-1 Antigen / Q000378:metabolism; D018106:CD28 Antigens / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010950:Plasma Cells / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D018106:CD28 Antigens; D019869:Phosphatidylinositol 3-Kinases