IMMUNOBIOLOGY b2-Microglobulin Identified as an Apoptosis-Inducing Factor and Its Characterization

Major histocompatibility complex (MHC) molecules play an important role in antigen presentation for induction of tumor as well as cellular and humoral immunities. Recent studies using anti-MHC antibodies demonstrated that antibodies specific for HLA class I molecules induced cellular activation and a type of apoptosis that may be distinct from Fas-dependent or TNFR (tumor necrosis factor-a receptor)-dependent processes. We purified a previously untested apoptosis-inducing factor from HL-60 human leukemic cell-conditioned media to homogeneity and sequenced it. It was identified as b2-microglobulin (b2m), which has been previ-ously known as thymotaxin and is a part of the HLA class I antigen complex. b2m acts on both T-leukemic cells and myeloid leukemic cells to induce apoptosis, which then activates caspase 1 and 3. Cross-linking studies showed tha