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Blood, Vol. 94 No. 8 (October 15), 1999:
pp. 2744-2753
 2-Microglobulin Identified as an Apoptosis-Inducing
Factor and Its Characterization
Masaki Mori,
Yasuhito Terui,
Masayuki Ikeda,
Hiroshi Tomizuka,
Masaya Uwai,
Tadashi Kasahara,
Nobuyuki Kubota,
Takehito Itoh,
Yuji Mishima,
Miyuki Douzono-Tanaka,
Muneo Yamada,
Seiichi Shimamura,
Jiro Kikuchi,
Yusuke Furukawa,
Yukihito Ishizaka,
Kazuma Ikeda,
Hiroyuki Mano,
Keiya Ozawa, and
Kiyohiko Hatake
From the Department of Hematology and the Divisions of Molecular
Hematopoiesis and of Genetic Therapeutics, Center for Molecular
Medicine, Jichi Medical School, Tochigi, Japan; the Biochemical
Research Laboratory, Morinaga Milk Industry Co Ltd, Kanagawa, Japan;
the Department of Biochemistry, Kyouritsu Pharmaceutical College,
Tokyo, Japan; the Immunochemistry System Department, Eiken Chemical Co
Ltd, Tochigi, Japan; the Department of Intractable Diseases,
International Medical Center of Japan, Tokyo, Japan; and the Department
of Transfusion, University of Okayama, Okayama, Japan.
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- 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  2-microglobulin
(2m), which has been previously known as thymotaxin and
is a part of the HLA class I antigen complex. 2m acts on
both T-leukemic cells and myeloid leukemic cells to induce apoptosis,
which then activates caspase 1 and 3. Cross-linking studies showed that
biotinilated 2m recognized an epitope distinct from
those recognized by the anti-HLA class I antibody, as reported previously. We demonstrated that 2m plays a previously
unrecognized and important role in regulating the elimination of tumor
cells, which occurs as a result of the action of 2m as
an apoptosis-inducing factor.
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