C-X-C chemokine receptor type 5 (CXC-R5) also known as CD185 (
cluster of differentiation 185) or Burkitt lymphoma receptor 1 (BLR1) is a
G protein-coupled seven transmembrane receptor for chemokine
CXCL13 (also known as BLC) and belongs to the
CXC chemokine receptor
CXC chemokine receptors are integral membrane proteins that specifically bind and respond to cytokines of the CXC chemokine family. They represent one subfamily of chemokine receptors, a large family of G protein-linked receptors that are k ...
family. It enables T cells to migrate to lymph node and the B cell zones. In humans, the CXC-R5 protein is encoded by the ''CXCR5''
gene.
Tissue distribution and function
The ''BLR1'' / ''CXCR5''
gene is specifically expressed in
Burkitt's lymphoma
Burkitt lymphoma is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center. It is named after Denis Parsons Burkitt, the Irish surgeon who first described the disease in 1958 while working in equatorial Africa. ...
and lymphatic tissues, such as follicles in
lymph nodes as well as in
spleen. The gene plays an essential role in
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 ...
migration.
Through CXCL13 secretions B cells are able to locate the lymph node.
Additionally, some recent studies have suggested that CXCL13, through CXCR5, is capable of recruiting hematopoietic precursor cells (CD3
− CD4
+) which would cause the development of
lymph node
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
s and
Peyer's Patches.
Other studies highlight the role of CXCR5 in T cells, as they are unable to access B cell follicles without CXCR5 expression.
This is a key step in the production of high affinity
antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
as B cells and T cells need to interact in order to activate the Ig class switch.
CXCR5 has been shown to be expressed on both
CD4
In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic ...
and
CD8 T cells, though it is often regarded as the defining marker for T Follicular Helper (Tfh) cells.
Role in cancer development
Recently, it was shown that CXCR5 overexpression in breast cancer patients highly correlates with lymph node metastases,
and elevated CXCR5 expression may contribute to abnormal cell survival and migration in breast tumors that lack functional
p53 protein.
Minor allele of
SNP rs630923, located in the area of CXCR5 gene promoter and associated with the risk of
multiple sclerosis
Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...
, is responsible for appearance of
MEF2C-binding site resulted in reduced CXCR5 gene promoter activity in B-cells during activation, that could lead to decreased autoimmune response
While chemokines and chemokine receptors have been thought to be involved in cancer development and maintenance, recently CXCR5 has come under investigation for its role in metastatic progression of prostate cancer. A recent study has indicated that prostate cancer tissue as well as cell lines express higher non-basal levels of CXCR5.
Furthermore, the study found a correlation between the level of CXCR5 and
Gleason score. CXCR5 location was additionally considered and higher Gleason scores correlated with nuclear CXCR5 while cytoplasmic and membrane CXCR5 correlated with benign and early prostate cancers.
References
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Clusters of differentiation
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