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 family. It enables T cells to migrate to lymph node B cell zones. In humans, the CXC-R5 protein is encoded by the CXCR5gene.[1]
The BLR1 / CXCR5gene is specifically expressed in Burkitt's lymphoma and lymphatic tissues, such as follicles in lymph nodes as well as in spleen. The gene plays an essential role in B cell migration.[2] Recently, it was shown that CXCR5 overexpression in breast cancer patients highly correlates with lymph node metastases,[3] and elevated CXCR5 expression may contribute to abnormal cell survival and migration in breast tumors that lack functional p53 protein.[4] 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-binding site resulted in reduced CXCR5 gene promoter activity in B-cells during activation, that could lead to decreased autoimmune response [5]
References
↑Dobner T, Wolf I, Emrich T, Lipp M (November 1992). "Differentiation-specific expression of a novel G protein-coupled receptor from Burkitt's lymphoma". European Journal of Immunology. 22 (11): 2795–9. doi:10.1002/eji.1830221107. PMID1425907.
↑Förster R, Mattis AE, Kremmer E, Wolf E, Brem G, Lipp M (December 1996). "A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen". Cell. 87 (6): 1037–47. doi:10.1016/S0092-8674(00)81798-5. PMID8978608.
↑Biswas S, Sengupta S, Roy Chowdhury S, Jana S, Mandal G, Mandal PK, Saha N, Malhotra V, Gupta A, Kuprash DV, Bhattacharyya A (January 2014). "CXCL13-CXCR5 co-expression regulates epithelial to mesenchymal transition of breast cancer cells during lymph node metastasis". Breast Cancer Res Treat. 143 (2): 265–76. doi:10.1007/s10549-013-2811-8. PMID24337540.
Lipp M, Müller G (2006). "Shaping up adaptive immunity: the impact of CCR7 and CXCR5 on lymphocyte trafficking". Verhandlungen Der Deutschen Gesellschaft Für Pathologie. 87: 90–101. PMID16888899.
Gunn MD, Ngo VN, Ansel KM, Ekland EH, Cyster JG, Williams LT (February 1998). "A B-cell-homing chemokine made in lymphoid follicles activates Burkitt's lymphoma receptor-1". Nature. 391 (6669): 799–803. doi:10.1038/35876. PMID9486651.
Müller G, Lipp M (September 2001). "Signal transduction by the chemokine receptor CXCR5: structural requirements for G protein activation analyzed by chimeric CXCR1/CXCR5 molecules". Biological Chemistry. 382 (9): 1387–97. doi:10.1515/BC.2001.171. PMID11688722.
Schaerli P, Loetscher P, Moser B (December 2001). "Cutting edge: induction of follicular homing precedes effector Th cell development". Journal of Immunology. 167 (11): 6082–6. doi:10.4049/jimmunol.167.11.6082. PMID11714765.
Kim CH, Johnston B, Butcher EC (July 2002). "Trafficking machinery of NKT cells: shared and differential chemokine receptor expression among V alpha 24(+)V beta 11(+) NKT cell subsets with distinct cytokine-producing capacity". Blood. 100 (1): 11–6. doi:10.1182/blood-2001-12-0196. PMID12070001.
Battle TE, Yen A (October 2002). "Ectopic expression of CXCR5/BLR1 accelerates retinoic acid- and vitamin D(3)-induced monocytic differentiation of U937 cells". Experimental Biology and Medicine. 227 (9): 753–62. doi:10.1177/153537020222700906. PMID12324654.
Lisignoli G, Toneguzzi S, Piacentini A, Cattini L, Lenti A, Tschon M, Cristino S, Grassi F, Facchini A (January 2003). "Human osteoblasts express functional CXC chemokine receptors 3 and 5: activation by their ligands, CXCL10 and CXCL13, significantly induces alkaline phosphatase and beta-N-acetylhexosaminidase release". Journal of Cellular Physiology. 194 (1): 71–9. doi:10.1002/jcp.10188. PMID12447991.
Chan CC, Shen D, Hackett JJ, Buggage RR, Tuaillon N (February 2003). "Expression of chemokine receptors, CXCR4 and CXCR5, and chemokines, BLC and SDF-1, in the eyes of patients with primary intraocular lymphoma". Ophthalmology. 110 (2): 421–6. doi:10.1016/S0161-6420(02)01737-2. PMID12578791.
Flynn G, Maru S, Loughlin J, Romero IA, Male D (March 2003). "Regulation of chemokine receptor expression in human microglia and astrocytes". Journal of Neuroimmunology. 136 (1–2): 84–93. doi:10.1016/S0165-5728(03)00009-2. PMID12620646.
Lisignoli G, Piacentini A, Toneguzzi S, Grassi F, Tschon M, Cristino S, Facchini A, Mariani E (2004). "Age-associated changes in functional response to CXCR3 and CXCR5 chemokine receptors in human osteoblasts". Biogerontology. 4 (5): 309–17. doi:10.1023/A:1026203502385. PMID14618028.
Aust G, Sittig D, Becherer L, Anderegg U, Schütz A, Lamesch P, Schmücking E (February 2004). "The role of CXCR5 and its ligand CXCL13 in the compartmentalization of lymphocytes in thyroids affected by autoimmune thyroid diseases". European Journal of Endocrinology / European Federation of Endocrine Societies. 150 (2): 225–34. doi:10.1530/eje.0.1500225. PMID14763921.
Steinmetz OM, Panzer U, Kneissler U, Harendza S, Lipp M, Helmchen U, Stahl RA (April 2005). "BCA-1/CXCL13 expression is associated with CXCR5-positive B-cell cluster formation in acute renal transplant rejection". Kidney International. 67 (4): 1616–21. doi:10.1111/j.1523-1755.2005.00244.x. PMID15780119.
Hu C, Xiong J, Zhang L, Huang B, Zhang Q, Li Q, Yang M, Wu Y, Wu Q, Shen Q, Gao Q, Zhang K, Sun Z, Liu J, Jin Y, Tan J (August 2004). "PEG10 activation by co-stimulation of CXCR5 and CCR7 essentially contributes to resistance to apoptosis in CD19+CD34+ B cells from patients with B cell lineage acute and chronic lymphocytic leukemia". Cellular & Molecular Immunology. 1 (4): 280–94. PMID16225771.
