Editing CD32

{{short description|Surface receptor glycoprotein}}
{{about|the molecule|the video game console|Amiga CD32}}

{{infobox protein
|Name= [[FCGR2A|Fc fragment of IgG, low affinity IIa, receptor (CD32)]]
|caption=
|image=
|width=
|HGNCid=3616
|Symbol=[[FCGR2A]]
|AltSymbols=FCG2, FCGR2A1, FCGR2
|EntrezGene=2212
|OMIM=146790
|RefSeq=NM_021642
|UniProt=P12318
|PDB=
|ECnumber=
|Chromosome=1
|Arm=q
|Band=23
|LocusSupplementaryData=
}}
{{infobox protein
|Name= [[FCGR2B|Fc fragment of IgG, low affinity IIb, receptor (CD32)]]
|caption=Crystal structure of the human fcgamma-receptor IIb ectodomain (CD32).<ref name="pmid10064577">{{PDB|2FCB}}; {{cite journal | vauthors = Sondermann P, Huber R, Jacob U | title = Crystal structure of the soluble form of the human fcgamma-receptor IIb: a new member of the immunoglobulin superfamily at 1.7 A resolution | journal = The EMBO Journal | volume = 18 | issue = 5 | pages = 1095–103 | date = March 1999 | pmid = 10064577 | pmc = 1171201 | doi = 10.1093/emboj/18.5.1095 }}; rendered via [http://pymol.sourceforge.net PyMOL].</ref>
|image=CD32ray.png
|width=
|HGNCid=3618
|Symbol=[[FCGR2B]]
|AltSymbols=FCG2, FCGR2
|EntrezGene=2213
|OMIM=604590
|RefSeq=NM_004001
|UniProt=P31994
|PDB=
|ECnumber=
|Chromosome=1
|Arm=q
|Band=23
|LocusSupplementaryData=
}}
{{infobox protein
|Name=Fc fragment of IgG, low affinity IIc, receptor for (CD32)
|caption=
|image=
|width=
|HGNCid=15626
|Symbol=FCGR2C
|AltSymbols=
|EntrezGene=9103
|OMIM=
|RefSeq=NM_201563
|UniProt=P31995
|PDB=
|ECnumber=
|Chromosome=1
|Arm=q
|Band=23
|LocusSupplementaryData=
}}
'''CD32''' ('''c'''luster of '''d'''ifferentiation 32), also known as '''FcγRII''' or '''FCGR2''', is a surface receptor [[glycoprotein]] belonging to the Ig gene superfamily.<ref name=":0">{{cite journal | vauthors = Lisi S, Sisto M, Lofrumento DD, D'Amore S, D'Amore M | title = Advances in the understanding of the Fc gamma receptors-mediated autoantibodies uptake | journal = Clinical and Experimental Medicine | volume = 11 | issue = 1 | pages = 1–10 | date = March 2011 | pmid = 20454994 | doi = 10.1007/s10238-010-0098-1 | s2cid = 6748965 }}</ref> CD32 can be found on the surface of a variety of immune cells.<ref name=":0" /><ref name=":1">{{cite journal | vauthors = Anania JC, Chenoweth AM, Wines BD, Hogarth PM | title = The Human FcγRII (CD32) Family of Leukocyte FcR in Health and Disease | language = English | journal = Frontiers in Immunology | volume = 10 | pages = 464 | date = 2019 | pmid = 30941127 | pmc = 6433993 | doi = 10.3389/fimmu.2019.00464 | doi-access = free }}</ref> CD32 has a low-affinity for the [[Fragment crystallizable region|Fc region]] of [[Immunoglobulin G|IgG]] antibodies in monomeric form, but high affinity for IgG [[immune complex]]es.<ref name=":3">{{cite journal | vauthors = Hamzeh-Cognasse H, Damien P, Chabert A, Pozzetto B, Cognasse F, Garraud O | title = Platelets and infections - complex interactions with bacteria | journal = Frontiers in Immunology | volume = 6 | pages = 82 | date = 2015-02-26 | pmid = 25767472 | pmc = 4341565 | doi = 10.3389/fimmu.2015.00082 | doi-access = free }}</ref> CD32 has two major functions: cellular response regulation, and the uptake of immune complexes.<ref name=":0" /> Cellular responses regulated by CD32 include [[phagocytosis]], [[cytokine]] stimulation, and [[Endocytosis|endocytic transport]].<ref name=":1" /> Dysregulated CD32 is associated with different forms of [[autoimmunity]], including [[systemic lupus erythematosus]].<ref name=":2">{{cite journal | vauthors = Smith KG, Clatworthy MR | title = FcgammaRIIB in autoimmunity and infection: evolutionary and therapeutic implications | journal = Nature Reviews. Immunology | volume = 10 | issue = 5 | pages = 328–43 | date = May 2010 | pmid = 20414206 | pmc = 4148599 | doi = 10.1038/nri2762 }}</ref> 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.<ref name=":1" />

== Structure and signaling ==
CD32 is a [[type I transmembrane protein]] with a helical transmembrane region.<ref name=":0" /> Whereas the extracellular region consists of three [[immunoglobulin domain]]s (roughly 100 a.a. in length), the cytosolic region varies by subtype. CD32A and CD32C possess an [[immunoreceptor tyrosine-based activation motif]] (ITAM), while CD32B has an [[immunoreceptor tyrosine-based inhibitory motif]] (ITIM). Both motif types rely upon interactions with [[SH2 domain|SH2 domain-containing proteins]] to transduce signals upon binding to an IgG immune complex. When an ITIM is [[Phosphorylation|phosphorylated]], it activates effector proteins that dephosphorylate the downstream targets of the ITAM signal cascade, such as [[Map kinase|MAP kinases]].<ref name=":1" /><ref name=":2" />

CD32 receptors bind to the [[Antibody|lower hinge region]] of IgG via an extracellular domain. Additionally, all CD32 subtypes readily bind [[IgG1]] and [[IgG3]] immune complexes, but differ in their binding affinities for [[IgG2]] and [[IgG4]]. CD32A binds IgG2 immune complexes, but not IgG4. CD32B and CD32C bind IgG4 immune complexes, but not IgG2. The usage of [[Monoclonal antibody|monoclonal antibodies]] can distinguish between CD32A and CD32B;<ref name="pmid17386079">{{cite journal | vauthors = Veri MC, Gorlatov S, Li H, Burke S, Johnson S, Stavenhagen J, Stein KE, Bonvini E, Koenig S | display-authors = 6 | title = Monoclonal antibodies capable of discriminating the human inhibitory Fcgamma-receptor IIB (CD32B) from the activating Fcgamma-receptor IIA (CD32A): biochemical, biological and functional characterization | journal = Immunology | volume = 121 | issue = 3 | pages = 392–404 | date = July 2007 | pmid = 17386079 | pmc = 2265948 | doi = 10.1111/j.1365-2567.2007.02588.x }}</ref> 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]]s, [[neutrophil]]s, [[macrophage]]s, and [[dendritic cell]]s (DCs). On platelets, it is known to aid in the internalization of IgG-[[Opsonin|opsonized]] ''[[Escherichia coli]]'', and it is more generally implicated in mediating bacterial-activated platelet responses.<ref name=":3" /> CD32A also plays an important role in platelet activation, adhesion, and aggregation in response to injured blood vessels.<ref name=":1" /> When bound to an IgG immune complex, the cytosolic ITAM can promote [[Phagocytosis|phagocytic activity]] and [[Cytokine|cytokine secretion]] in neutrophils and macrophages.<ref name=":0" /> CD32A is known to aid in the activation of [[Clathrin|clathrin coat]]-mediated endocytosis on various cell types. On DCs, CD32A plays an important role in maturation and the upregulation of [[B7 (protein)|costimulatory molecules]] on the cell surface, strengthening the DC's ability to [[Antigen presentation|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]]; for example, the production of antibodies against [[platelet factor 4]] (PF4) bound to CD32A is linked to the development of [[heparin-induced thrombocytopenia]].<ref name=":3" />

CD32A is also found on [[Langerhans cell|Langerhans]] cells, [[mast cell]]s, [[basophil]]s, [[eosinophil]]s, [[monocyte]]s, [[megakaryocyte]]s, and a subpopulation of activated [[T helper cell|CD4+ T cells]]. CD32A is unique to primates.<ref name=":1" />

=== ''CD32B'' ===
CD32B is an inhibitory surface receptor that is part of a large population of [[B cell]] co-receptors, which act to modulate signaling.<ref name=":1" /> Activated CD32B has the ability to cross-link with [[B-cell receptor|B cell receptors]] (BCRs), which increases the threshold for B cell activation and downregulates antibody production in the presence of IgG.<ref name=":2" /> 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]] (FDCs), which utilize CD32B for the retention and recycling of immune complexes that they later present to B cells.<ref name=":1" /><ref name=":4">{{cite journal | vauthors = Hill DL, Schofield L, Wilson DW | title = IgG opsonization of merozoites: multiple immune mechanisms for malaria vaccine development | journal = International Journal for Parasitology | volume = 47 | issue = 10–11 | pages = 585–595 | date = September 2017 | pmid = 28668325 | doi = 10.1016/j.ijpara.2017.05.004 }}</ref> Thus, CD32B plays an important role in both antibody and [[Immunological memory|memory immune responses]].<ref name=":1" />

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.<ref name=":1" /> 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.<ref name=":4" /> 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]]s. A decrease on dendritic cells is often found in patients with [[rheumatoid arthritis]].<ref name=":0" /><ref name=":2" /> The therapeutic usage of monoclonal antibodies against CD32B can be effective for inducing cytotoxicity against [[B-cell lymphoma|B cell lymphoma]] cells.<ref name=":1" />

CD32B is also found on basophils, neutrophils, monocytes, and macrophages.<ref name=":0" />

==== Non-immune system locations ====
CD32B can be found on airway [[smooth muscle]] cells, as well as [[liver sinusoidal endothelial cell]]s and [[salivary gland]] epithelial cells.<ref name=":1" /><ref name=":4" />

=== ''CD32C'' ===
CD32C is expressed in ~20% of the human population, and is not well-understood.<ref name=":0" /> It can be found on B cells and [[Natural killer cell|natural killer]] (NK) cells. When expressed, CD32C plays an important role in the activation of [[Antibody-dependent cellular cytotoxicity|antibody-dependent cell cytotoxicity]] (ADCC).<ref name=":1" /> Animal studies have linked CD32C to augmentation of pathological inflammatory responses.<ref name=":1" />

== See also ==

* [[FCGR2A]]
* [[FCGR2B]]
* [[Fc fragment of igg receptor iic (gene/pseudogene)|FCGR2C]]
* [[Fc-gamma receptor]]s

== References ==
{{reflist}}

== External links ==
* {{MeshName|CD32+Antigens}}

{{Clusters of differentiation}}
{{Immune receptors}}

[[Category:Clusters of differentiation]]
[[Category:Fc receptors]]