β
2 microglobulin (B2M) is a component of
MHC class I molecules. MHC class I molecules have α
1, α
2, and α
3 proteins which are present on all nucleated cells (excluding
red blood cell
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
s).
In humans, the β
2 microglobulin
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
is encoded by the ''B2M''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Structure and function
β
2 microglobulin lies beside the α
3 chain on the cell surface. Unlike α
3, β
2 has no
transmembrane
A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequent ...
region. Directly above β
2 (that is, further away from the cell) lies the α
1 chain, which itself is next to the α
2.
β
2 microglobulin associates not only with the alpha chain of MHC class I molecules, but also with class I-like molecules such as
CD1
CD1 (cluster of differentiation 1) is a family of glycoproteins expressed on the surface of various human antigen-presenting cells. They are related to the class I MHC molecules, and are involved in the presentation of lipid antigens to T ...
(5 genes in humans),
MR1, the
neonatal Fc receptor
The neonatal Fc receptor (also FcRn, IgG receptor FcRn large subunit p51, or Brambell receptor) is a protein that in humans is encoded by the ''FCGRT'' gene. It is an IgG Fc receptor which is similar in structure to the MHC class I molecule an ...
(FcRn), and Qa-1 (a form of
alloantigen). Nevertheless, the β
2 microglobulin gene is outside of the MHC (HLA) locus, on a different chromosome.
An additional function is association with the
HFE protein, together regulating the expression of
hepcidin
Hepcidin is a protein that in humans is encoded by the ''HAMP'' gene. Hepcidin is a key regulator of the entry of iron into the circulation in mammals.
During conditions in which the hepcidin level is abnormally high, such as inflammation, se ...
in the
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
which targets the iron transporter
ferroportin
Ferroportin-1, also known as solute carrier family 40 member 1 (SLC40A1) or iron-regulated transporter 1 (IREG1), is a protein that in humans is encoded by the ''SLC40A1'' gene, and is part of the Ferroportin (Fpn) FamilyTC# 2.A.100. Ferroportin i ...
on the basolateral membrane of
enterocytes
Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase it ...
and cell membrane of
macrophages
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
for degradation resulting in decreased iron uptake from food and decreased iron release from recycled red blood cells in the MPS (mononuclear phagocyte system) respectively. Loss of this function causes iron excess and
hemochromatosis
Iron overload or hemochromatosis (also spelled ''haemochromatosis'' in British English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatos ...
.
In a
cytomegalovirus infection, a viral protein binds to β
2 microglobulin, preventing assembly of MHC class I molecules and their transport to the plasma membrane.
Mice models deficient for the β
2 microglobulin gene have been engineered. These mice demonstrate that β
2 microglobulin is necessary for cell surface expression of MHC class I and stability of the peptide-binding groove. In fact, in the absence of β
2 microglobulin, very limited amounts of MHC class I (classical and non-classical) molecules can be detected on the surface (
bare lymphocyte syndrome
Bare lymphocyte syndrome is a condition caused by mutations in certain genes of the major histocompatibility complex or involved with the processing and presentation of MHC molecules. It is a form of severe combined immunodeficiency.
Presentati ...
or BLS). In the absence of MHC class I,
CD8
CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). Along with the TCR, the CD8 co-receptor plays a role in T cell signaling and aiding with cytotoxic T cell-antigen int ...
+ T cells cannot develop. (CD8
+ T cells are a subset of T cells involved in the development of acquired immunity.)
Clinical significance
In patients on long-term
hemodialysis
Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatinin ...
, it can aggregate into
amyloid
Amyloids are aggregates of proteins characterised by a fibrillar morphology of 7–13 nm in diameter, a beta sheet (β-sheet) secondary structure (known as cross-β) and ability to be stained by particular dyes, such as Congo red. In the huma ...
fibers that deposit in joint spaces, a disease, known as
dialysis-related amyloidosis
Amyloidosis is the accumulation on misfolded protein fibers in the body. This is very common condition associated with many of the chronic illness.
Haemodialysis-associated amyloidosis is a form of systemic amyloidosis associated with chronic k ...
.
Low levels of β
2 microglobulin can indicate non-progression of HIV.
Levels of β
2 microglobulin can be elevated in
multiple myeloma and
lymphoma
Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enla ...
, though in these cases primary amyloidosis (amyloid light chain) and secondary amyloidosis (amyloid associated protein) are more common. The normal value of β
2 microglobulin is < 2 mg/L.
However, with respect to multiple myeloma, the levels of β
2 microglobulin may also be at the other end of the spectrum. Diagnostic testing for multiple myeloma includes obtaining the β
2 microglobulin level, for this level is an important prognostic indicator. , a patient with a level < 4 mg/L is expected to have a median survival of 43 months, while one with a level > 4 mg/L has a median survival of only 12 months.
β
2 microglobulin levels cannot, however, distinguish between
monoclonal gammopathy of undetermined significance
Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia in which plasma cells or other types of antibody-producing cells secrete a myeloma protein, i.e. an abnormal antibody, into the blood; this abnormal protein is ...
(MGUS), which has a better prognosis, and ''smouldering'' (low grade) myeloma.
Loss-of-function mutations in this gene have been reported in cancer patients unresponsive to immunotherapies.
References
Further reading
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External links
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{{DEFAULTSORT:Beta-2 Microglobulin
Proteins
Immune system