CD32
   HOME

TheInfoList



OR:

CD32 (cluster of differentiation 32), also known as FcγRII or FCGR2, is a surface receptor glycoprotein belonging to the Ig gene superfamily. CD32 can be found on the surface of a variety of immune cells. CD32 has a low-affinity for the
Fc region The fragment crystallizable region (Fc region) is the tail region of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of the complement system. This property allows antibodies to activate the immune s ...
of
IgG Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...
antibodies in monomeric form, but high affinity for IgG
immune complex An immune complex, sometimes called an antigen-antibody complex or antigen-bound antibody, is a molecule formed from the binding of multiple antigens to antibodies. The bound antigen and antibody act as a unitary object, effectively an antigen o ...
es. CD32 has two major functions: cellular response regulation, and the uptake of immune complexes. Cellular responses regulated by CD32 include
phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is ...
,
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
stimulation, and endocytic transport. Dysregulated CD32 is associated with different forms of
autoimmunity In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". ...
, including systemic lupus erythematosus. In humans, there are three major CD32 subtypes: CD32A, CD32B, and CD32C. While CD32A and CD32C are involved in activating cellular responses, CD32B is inhibitory.


Structure and signaling

CD32 is a type I transmembrane protein with a helical transmembrane region. Whereas the extracellular region consists of three
immunoglobulin domain The immunoglobulin domain, also known as the immunoglobulin fold, is a type of protein domain that consists of a 2-layer sandwich of 7-9 antiparallel β-strands arranged in two β-sheets with a Greek key topology, consisting of about 125 amino a ...
s (roughly 100 a.a. in length), the cytosolic region varies by subtype. CD32A and CD32C possess an
immunoreceptor tyrosine-based activation motif An immunoreceptor tyrosine-based activation motif (ITAM) is a conserved sequence of four amino acids that is repeated twice in the cytoplasmic tails of non-catalytic tyrosine-phosphorylated receptors, cell-surface proteins found mainly on immune ce ...
(ITAM), while CD32B has an
immunoreceptor tyrosine-based inhibitory motif An immunoreceptor tyrosine-based inhibitory motif (ITIM), is a conserved sequence of amino acids that is found intracellularly in the cytoplasmic domains of many inhibitory receptors of the non-catalytic tyrosine-phosphorylated receptor family fou ...
(ITIM). Both motif types rely upon interactions with SH2 domain-containing proteins to transduce signals upon binding to an IgG immune complex. When an ITIM is
phosphorylated In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
, it activates effector proteins that dephosphorylate the downstream targets of the ITAM signal cascade, such as
MAP kinases A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine and threonine (i.e., a serine/threonine-specific protein kinase). MAPKs are involved in directing cellular responses ...
. CD32 receptors bind to the lower hinge region of IgG via an extracellular domain. Additionally, all CD32 subtypes readily bind
IgG1 Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...
and IgG3 immune complexes, but differ in their binding affinities for
IgG2 Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...
and
IgG4 Immunoglobulin G (Ig G) is a Antibody#Classes, type of antibody. Representing approximately 75% of blood plasma, serum immunoglobulins, antibodies in humans, IgG is the most common type of antibody found in Circulatory system, blood circulation. I ...
. CD32A binds IgG2 immune complexes, but not IgG4. CD32B and CD32C bind IgG4 immune complexes, but not IgG2. The usage of monoclonal antibodies can distinguish between CD32A and CD32B; however, the high degree of homology between the extracellular domains of CD32A and CD32C make differentiation difficult.


Functions and locations


''CD32A''

CD32A is an activating subtype of CD32 that can be found on a variety of immune cells - notably, CD32A is found on
platelet Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...
s,
neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...
s, macrophages, and dendritic cells (DCs). On platelets, it is known to aid in the internalization of IgG- opsonized ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
'', and it is more generally implicated in mediating bacterial-activated platelet responses. CD32A also plays an important role in platelet activation, adhesion, and aggregation in response to injured blood vessels. When bound to an IgG immune complex, the cytosolic ITAM can promote phagocytic activity and cytokine secretion in neutrophils and macrophages. CD32A is known to aid in the activation of clathrin coat-mediated endocytosis on various cell types. On DCs, CD32A plays an important role in maturation and the upregulation of costimulatory molecules on the cell surface, strengthening the DC's ability to present antigen to T cells. CD32A activation is necessary and sufficient to produce T cell anti-tumor cellular immunity. CD32A is also linked to
autoimmunity In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". ...
; for example, the production of antibodies against
platelet factor 4 Platelet factor 4 (PF4) is a small cytokine belonging to the CXC chemokine family that is also known as chemokine (C-X-C motif) ligand 4 (CXCL4) . This chemokine is released from alpha-granules of activated platelets during platelet aggregation, ...
(PF4) bound to CD32A is linked to the development of
heparin-induced thrombocytopenia Heparin-induced thrombocytopenia (HIT) is the development of thrombocytopenia (a low platelet count), due to the administration of various forms of heparin, an anticoagulant. HIT predisposes to thrombosis (the abnormal formation of blood clots ...
. CD32A is also found on Langerhans cells,
mast cell A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a par ...
s,
basophil Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammator ...
s,
eosinophil Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...
s,
monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also inf ...
s,
megakaryocyte A megakaryocyte (''mega-'' + '' karyo-'' + '' -cyte'', "large-nucleus cell") is a large bone marrow cell with a lobated nucleus responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting. In hum ...
s, and a subpopulation of activated
CD4+ T cells The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are consider ...
. CD32A is unique to primates.


''CD32B''

CD32B is an inhibitory surface receptor that is part of a large population of
B cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
co-receptors, which act to modulate signaling. Activated CD32B has the ability to cross-link with B cell receptors (BCRs), which increases the threshold for B cell activation and downregulates antibody production in the presence of IgG. This feedback loop lowers the production of IgG by B cells when there is a surplus of IgG in the body. CD32B is also found on the surface of
follicular dendritic cells Follicular dendritic cells (FDC) are cells of the immune system found in primary and secondary lymph follicles (lymph nodes) of the B cell areas of the lymphoid tissue. Unlike dendritic cells (DC), FDCs are not derived from the bone-marrow hema ...
(FDCs), which utilize CD32B for the retention and recycling of immune complexes that they later present to B cells. Thus, CD32B plays an important role in both antibody and memory immune responses. The balance between CD32B and its activating counterparts is crucial to appropriate cell function. Having too little CD32B has been associated with dysregulated antibody function, as well as increased antibody-dependent inflammatory cell responses. Some individuals inheriting mutated, inactivate CD32B genes have a reduced risk of contracting malaria; this is attributed to an enhancement of FcR-dependent phagocytic functions. CD32B imbalance is also associated with autoimmunity. CD32B-deficient mice have been found to be more susceptible to immune-complex-mediated autoimmunity. Likewise, systemic lupus erythematosus (SLE) in humans is associated with a decrease in CD32B on the surface of
memory B cell In immunology, a memory B cell (MBC) is a type of B lymphocyte that forms part of the adaptive immune system. These cells develop within germinal centers of the secondary lymphoid organs. Memory B cells circulate in the blood stream in a quiescen ...
s. A decrease on dendritic cells is often found in patients with
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...
. The therapeutic usage of monoclonal antibodies against CD32B can be effective for inducing cytotoxicity against B cell lymphoma cells. CD32B is also found on basophils, neutrophils, monocytes, and macrophages.


Non-immune system locations

CD32B can be found on airway
smooth muscle Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...
cells, as well as
liver sinusoidal endothelial cell Liver sinusoidal endothelial cells (LSECs) form the lining of the smallest blood vessels in the liver, also called the hepatic sinusoids. LSECs are highly specialized endothelial cells with characteristic morphology and function. They constitute ...
s and
salivary gland The salivary glands in mammals are exocrine glands that produce saliva through a system of ducts. Humans have three paired major salivary glands (parotid, submandibular, and sublingual), as well as hundreds of minor salivary glands. Salivary gla ...
epithelial cells.


''CD32C''

CD32C is expressed in ~20% of the human population, and is not well-understood. It can be found on B cells and
natural killer Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represen ...
(NK) cells. When expressed, CD32C plays an important role in the activation of antibody-dependent cell cytotoxicity (ADCC). Animal studies have linked CD32C to augmentation of pathological inflammatory responses.


See also

*
FCGR2A Low affinity immunoglobulin gamma Fc region receptor II-a is a protein that in humans is encoded by the ''FCGR2A'' gene. Interactions FCGR2A has been shown to interact with PIK3R1 and Syk. See also * CD32 CD32 (cluster of differentiation 3 ...
* FCGR2B * FCGR2C * Fc-gamma receptors


References


External links

* {{Immune receptors Clusters of differentiation Fc receptors