CD11A-CD18 AND CD102 INTERACTIONS MEDIATE HUMAN MYELOMA CELL-GROWTH ARREST INDUCED BY CD40 STIMULATION

We have recently demonstrated that the CD40 molecule was expressed on both normal human plasma cells and most malignant plasma cells, i.e., myeloma cells. Thus, we have investigated its putative role in the pro liferation of myeloma cells. We report that 7 of lj myeloma cell lines were CD40(+) but only one, XG2, presented a high level of CD40 expres sion, We show that the CD40 stimulation by anti-CD40 monoclonal antibo dies (mAbs) of the interleukin 6-dependent myeloma cell line XG2 induc ed a total inhibition of its proliferation. This inhibition was also o bserved when cells were either cultured in the ''CD40 system,'' where the anti-CD40 mAb has been immobilized on fibroblasts expressing Fc re ceptors or in the presence of a soluble chimeric CD40 ligand molecule. This inhibition of proliferation was neither accompanied by different iation nor apoptosis. Triggering CD40 induced an homotypic aggregation of XG2 cells, and the inhibition of proliferation was totally prevent ed by a blocking anti-CD18 mAb. Although the CD11a-CD18 ligands, i.e., CD50, CD54, and CD102, were all expressed on XG2 cells, only a blocki ng anti-CD102 mAb inhibited the CD40-induced growth arrest. Our data d emonstrate that CD40 triggering on XG2 cells induced a myeloma cell gr owth arrest mediated by lymphocyte function-associated antigen 1 and i ntercellular adhesion molecule 2 interactions.