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Gene Review

Cxcr5  -  chemokine (C-X-C motif) receptor 5

Mus musculus

Synonyms: Blr1, Burkitt lymphoma receptor 1 homolog, C-X-C chemokine receptor type 5, CXC-R5, CXCR-5, ...
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Disease relevance of Blr1


High impact information on Blr1

  • Blr1 mutant mice lack inguinal lymph nodes and possess no or only a few phenotypically abnormal Peyer's patches [6].
  • Reciprocally, overexpression of CXCR5, the receptor for the B-zone chemokine CXCL13, is sufficient to overcome antigen-induced B-cell movement to the T zone [7].
  • CXC chemokine receptor-5 (CXCR5) is required for B-cell migration to splenic follicles, but the requirements for homing to B-cell areas in lymph nodes remain to be defined [8].
  • We show here that CXCR5/CXCL13 signaling activates alpha4beta1 integrin on CD4+CD3- cells [9].
  • CD4+CD3- cells induce Peyer's patch development: role of alpha4beta1 integrin activation by CXCR5 [9].

Biological context of Blr1

  • These data demonstrate a cooperative function of CXCR5 and CCR7 in lymphoid organ organogenesis and organization [10].
  • Herein, we analyzed the surface phenotype of skin-derived migratory DC and found that 15-35% of MHC class II(high) cells showed high levels of expression of CXCR5 but expressed low levels of DEC205, a suggested characteristic of dermal-type DC in mice [11].
  • CXCR5 was detected by flow cytometry on transduced cells, which responded to CXCL13 in vitro in chemotaxis assays (3-fold over nontransduced BMDC, p < 0.01) [11].
  • In addition, CCR7 and CXCR5 have been identified as useful markers in the classification of functionally distinct subsets of T-helper cells, which will lead to a better understanding of T cell memory and T cell effector function in lymphoid system homeostasis and disease [2].
  • Blr-1 consists of two exons encoding a protein of 374 amino acid residues which shows 83% identity with the human homologue [12].

Anatomical context of Blr1


Associations of Blr1 with chemical compounds

  • Here, we show markedly decreased B-1 B cell numbers in the peritoneal cavity of CXCR5-/- and CXCR5-/-CCR7-/- double-deficient mice paralleled by reduced antigen-induced phosphorylcholine-specific immunoglobulin (Ig)M responses after intraperitoneal (i.p.) administration of streptococcal antigen [15].

Regulatory relationships of Blr1

  • Compared to naïve, type-1 and type-2 populations had reduced CCR7 and enhanced CXCR5 transcripts, consistent with a shift to memory cells [16].

Other interactions of Blr1

  • We demonstrate that CD3- CD4+ IL-7R alpha hi cells express CXCR5 as well as CCR7 indicating that both receptors cooperate during an early step of secondary lymphoid organ development [10].
  • In addition, DN Treg cells have been shown to express several molecules uncommon to other Treg cell subsets, such as IFN-gamma, TNF-alpha, Ly6A, FcRgamma, and CXCR5, which may contribute to their unique regulatory ability [17].
  • Suppression of lymphotoxin signalling depleted FDCs, abolished splenic infectivity, and suppressed acceleration of pathogenesis in CXCR5-/- mice [18].
  • The chemokine receptor CXCR5 and its ligand CXCL13 define the structure of B cell follicles within secondary lymphoid organs [1].
  • Crucially, the up-regulation of OX40L (on antigen-presenting cells) and CXCR-5 (on T cells) are CD40-dependent events and we show that T cells do not migrate to follicles in immunized OX40-deficient mice [19].

Analytical, diagnostic and therapeutic context of Blr1


  1. CXCR5-dependent seeding of follicular niches by B and Th cells augments antiviral B cell responses. Junt, T., Fink, K., Förster, R., Senn, B., Lipp, M., Muramatsu, M., Zinkernagel, R.M., Ludewig, B., Hengartner, H. J. Immunol. (2005) [Pubmed]
  2. Systemic immunoregulatory and pathogenic functions of homeostatic chemokine receptors. Müller, G., Höpken, U.E., Stein, H., Lipp, M. J. Leukoc. Biol. (2002) [Pubmed]
  3. Role of homeostatic chemokine and sphingosine-1-phosphate receptors in the organization of lymphoid tissue. Müller, G., Reiterer, P., Höpken, U.E., Golfier, S., Lipp, M. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  4. An hour after immunization peritoneal B-1 cells are activated to migrate to lymphoid organs where within 1 day they produce IgM antibodies that initiate elicitation of contact sensitivity. Itakura, A., Szczepanik, M., Campos, R.A., Paliwal, V., Majewska, M., Matsuda, H., Takatsu, K., Askenase, P.W. J. Immunol. (2005) [Pubmed]
  5. OX40/OX40L interaction induces the expression of CXCR5 and contributes to chronic colitis induced by dextran sulfate sodium in mice. Obermeier, F., Schwarz, H., Dunger, N., Strauch, U.G., Grunwald, N., Schölmerich, J., Falk, W. Eur. J. Immunol. (2003) [Pubmed]
  6. A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen. Förster, R., Mattis, A.E., Kremmer, E., Wolf, E., Brem, G., Lipp, M. Cell (1996) [Pubmed]
  7. Balanced responsiveness to chemoattractants from adjacent zones determines B-cell position. Reif, K., Ekland, E.H., Ohl, L., Nakano, H., Lipp, M., Förster, R., Cyster, J.G. Nature (2002) [Pubmed]
  8. A chemokine-driven positive feedback loop organizes lymphoid follicles. Ansel, K.M., Ngo, V.N., Hyman, P.L., Luther, S.A., Förster, R., Sedgwick, J.D., Browning, J.L., Lipp, M., Cyster, J.G. Nature (2000) [Pubmed]
  9. CD4+CD3- cells induce Peyer's patch development: role of alpha4beta1 integrin activation by CXCR5. Finke, D., Acha-Orbea, H., Mattis, A., Lipp, M., Kraehenbuhl, J. Immunity (2002) [Pubmed]
  10. Cooperating mechanisms of CXCR5 and CCR7 in development and organization of secondary lymphoid organs. Ohl, L., Henning, G., Krautwald, S., Lipp, M., Hardtke, S., Bernhardt, G., Pabst, O., Förster, R. J. Exp. Med. (2003) [Pubmed]
  11. CXCR5-transduced bone marrow-derived dendritic cells traffic to B cell zones of lymph nodes and modify antigen-specific immune responses. Wu, M.T., Hwang, S.T. J. Immunol. (2002) [Pubmed]
  12. Selective expression of the murine homologue of the G-protein-coupled receptor BLR1 in B cell differentiation, B cell neoplasia and defined areas of the cerebellum. Förster, R., Wolf, I., Kaiser, E., Lipp, M. Cell. Mol. Biol. (Noisy-le-grand) (1994) [Pubmed]
  13. Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5. Allen, C.D., Ansel, K.M., Low, C., Lesley, R., Tamamura, H., Fujii, N., Cyster, J.G. Nat. Immunol. (2004) [Pubmed]
  14. Balanced expression of CXCR5 and CCR7 on follicular T helper cells determines their transient positioning to lymph node follicles and is essential for efficient B-cell help. Hardtke, S., Ohl, L., Förster, R. Blood (2005) [Pubmed]
  15. Distinct and overlapping roles of CXCR5 and CCR7 in B-1 cell homing and early immunity against bacterial pathogens. Höpken, U.E., Achtman, A.H., Krüger, K., Lipp, M. J. Leukoc. Biol. (2004) [Pubmed]
  16. Population analysis of CD4+ T cell chemokine receptor transcript expression during in vivo type-1 (mycobacterial) and type-2 (schistosomal) immune responses. Chiu, B.C., Shang, X.Z., Stolberg, V.R., Komuniecki, E., Chensue, S.W. J. Leukoc. Biol. (2002) [Pubmed]
  17. Double-Negative Regulatory T Cells: Non-conventional Regulators. Thomson, C.W., Lee, B.P., Zhang, L. Immunol. Res. (2006) [Pubmed]
  18. Positioning of follicular dendritic cells within the spleen controls prion neuroinvasion. Prinz, M., Heikenwalder, M., Junt, T., Schwarz, P., Glatzel, M., Heppner, F.L., Fu, Y.X., Lipp, M., Aguzzi, A. Nature (2003) [Pubmed]
  19. T cell accumulation in B cell follicles is regulated by dendritic cells and is independent of B cell activation. Fillatreau, S., Gray, D. J. Exp. Med. (2003) [Pubmed]
  20. The CXCR5 Chemokine Receptor Is Expressed by Carcinoma Cells and Promotes Growth of Colon Carcinoma in the Liver. Meijer, J., Zeelenberg, I.S., Sipos, B., Roos, E. Cancer Res. (2006) [Pubmed]
  21. Compromised OX40 function in CD28-deficient mice is linked with failure to develop CXC chemokine receptor 5-positive CD4 cells and germinal centers. Walker, L.S., Gulbranson-Judge, A., Flynn, S., Brocker, T., Raykundalia, C., Goodall, M., Förster, R., Lipp, M., Lane, P. J. Exp. Med. (1999) [Pubmed]
  22. Chemokine receptors in the rheumatoid synovium: upregulation of CXCR5. Schmutz, C., Hulme, A., Burman, A., Salmon, M., Ashton, B., Buckley, C., Middleton, J. Arthritis Res. Ther. (2005) [Pubmed]
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