C-X-C chemokine receptor type 5 (CXC-R5) also known as CD185 (
cluster of differentiation
The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophen ...
185) or Burkitt lymphoma receptor 1 (BLR1) is a
G protein-coupled
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
seven transmembrane receptor for chemokine
CXCL13
Chemokine (C-X-C motif) ligand 13 (CXCL13), also known as B lymphocyte chemoattractant (BLC) or B cell-attracting chemokine 1 (BCA-1), is a protein ligand that in humans is encoded by the ''CXCL13'' gene.
Function
CXCL13 is a small chemokine ...
(also known as BLC) and belongs to the
CXC chemokine receptor 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
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 ...
.
Tissue distribution and function
The ''BLR1'' / ''CXCR5''
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 ...
is specifically expressed in
Burkitt's lymphoma and lymphatic tissues, such as follicles in
lymph nodes
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 ...
as well as in
spleen
The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes . . The gene plays an essential role in
B cell 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 nodes and
Peyer's Patches
Peyer's patches (or aggregated lymphoid nodules) are organized lymphoid follicles, named after the 17th-century Swiss anatomist Johann Conrad Peyer.
* Reprinted as:
* Peyer referred to Peyer's patches as ''plexus'' or ''agmina glandularum'' (c ...
.
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 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 and
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, 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
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
protein.
Minor allele of
SNP rs630923, located in the area of CXCR5 gene promoter and associated with the risk of
multiple sclerosis, is responsible for appearance of
MEF2C
Myocyte-specific enhancer factor 2C also known as MADS box transcription enhancer factor 2, polypeptide C is a protein that in humans is encoded by the ''MEF2C'' gene. MEF2C is a transcription factor in the Mef2 family.
Genomics
The gene is l ...
-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
The Gleason grading system is used to help evaluate the prognosis of men with prostate cancer using samples from a prostate biopsy. Together with other parameters, it is incorporated into a strategy of prostate cancer staging which predicts prog ...
. 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
External links
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Further reading
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Clusters of differentiation
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