MHC class I-induced apoptosis in hematopoietic cells

The aims of this study have been focused on the identification of cell surface structures involved in the induction and regulation of apoptosis. Monoclonal antibodies against the major histocompatibility complex class I (MHC-I) were shown to induce apoptosis when cross-linked on the cell surface of different malignant cells having a pre-B or a myeloid precursor phenotype. The apoptotic response was not epitope dependent, since several different anti-MHC-I antibodies, reacting with different monomorphic determinants of MHC-I all induced apoptosis in these cells. However, external cross-linking of antibodies was strictly required for the apoptotic effect. Among cells originating from mature peripheral blood lymphocytes, anti-CD40 stimulated B-cells were susceptible to anti-MHC-I induced apoptosis, whereas resting as well as superantigen activated B- and T-cells were non-responsive to MHC-I ligation. The apoptotic process was not linked to protein kinase C activation or changes in cytoplasmic calcium concentration. In situ terminal deoxynucleotidyl transferase staining of apoptotic cells at various stages during MHC-I induced cell death revealed that apoptosis occurred predominantly in the G2/M phase of the cell cycle, with the first apoptotic cells appearing after approximately 12 hours of incubation. The results suggest a role for MHC-I mediated apoptosis during differentiation and activation of certain hematopoietic cells. (Less)