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Gene Review

Cxcl13  -  chemokine (C-X-C motif) ligand 13

Mus musculus

Synonyms: 4631412M08Rik, ANGIE2, Angie, B lymphocyte chemoattractant, BCA-1, ...
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Disease relevance of Cxcl13

  • These results indicate that aberrant B1 cell trafficking into the thymus due to ectopic high expression of BLC may result in an activation of self-reactive T cells in the development of murine lupus [1].
  • Intracerebral expression of CXCL13 and BAFF is accompanied by formation of lymphoid follicle-like structures in the meninges of mice with relapsing experimental autoimmune encephalomyelitis [2].
  • Our findings raise the possibility that reagents that antagonize or inhibit CXCL13 might be useful for the treatment of neuroinflammatory diseases such as multiple sclerosis [3].

High impact information on Cxcl13

  • In addition to mediating chemoattraction, BLC induces B cells to up-regulate membrane lymphotoxin alpha1beta2, a cytokine that promotes follicular dendritic cell development and BLC expression, establishing a positive feedback loop that is likely to be important in follicle development and homeostasis [4].
  • We also find that BLC is required for the development of most lymph nodes and Peyer's patches [4].
  • We show that BLC stimulates calcium influx into, and chemotaxis of, cells transfected with BLR-1 [5].
  • Here we show that FDC-specific expression of p55TNFR is necessary and sufficient to promote FDC network and B cell follicle formation, restore the expression of CXCL13 and VCAM-1/ICAM-1 in FDCs, and lead to productive GCs [6].
  • We show here that CXCR5/CXCL13 signaling activates alpha4beta1 integrin on CD4+CD3- cells [7].

Biological context of Cxcl13


Anatomical context of Cxcl13

  • However, unlike the NALT of Ltalpha(-/-) mice, the NALT of Cxcl13(-/-) mice has peripheral node addressin(+) high endothelial venules (HEVs) [12].
  • Functionally, germinal center formation and switching to IgA are defective in the NALT of Ltalpha(-/-) and Cxcl13(-/-) mice [12].
  • Like the NALT of Ltalpha(-/-) mice, the NALT in Cxcl13(-/-) mice lacks follicular dendritic cells, BP3(+) stromal cells, and ERTR7(+) lymphoreticular cells [12].
  • In germinal centres the feedback loop is overridden, with B-cell lymphotoxin alpha1beta2 expression being induced by a mechanism independent of BLC [4].
  • Surprisingly, TNF-alpha stimulation potently up-regulates cxcl13 mRNA expression in wild-type murine embryonic fibroblasts, which is impaired in traf2(-/-) and relA(-/-) murine embryonic fibroblasts [8].

Associations of Cxcl13 with chemical compounds

  • Importantly, lungs from all groups expressed CXCL13, CCL21, and CCL19 and displayed organized follicular neolymphoid structures after infection with M. tuberculosis, which suggests that the lung served as a selectin ligand-independent priming site for immune responses to mycobacterial infection [13].
  • Superfusion of CXCL13-null PPs with CXCL13 restored the luminal presentation of CXCL13 and also B cell arrest in PP HEVs at least partially [14].
  • CXCL13(-/-) mice are deficient in preexisting phosphorylcholine (PC)-specific antibodies and in their ability to mount an anti-PC response to peritoneal streptococcal antigen [15].
  • The major to minor product ratios of the 99mTc-labeled analogues were 3:1 for products from BCA 1 and 9:1 for the products from BCA 2 [16].
  • Wehn normal mouse spleen or lymph node cells are cultured for 7 days in agar-medium containing 2-mercaptoethanol and sheep red blood cells (SRBC), approximately one B lymphocyte colony (BLC) develops per 50-100 cells seeded [17].

Regulatory relationships of Cxcl13

  • BLC production was induced when PBL-DC were cultured in the presence of TNF-alpha for 3 days [18].
  • Altered localization of CXCL13 expressing cells in mice deficient in Pactolus following an inflammatory stimulus [19].

Other interactions of Cxcl13


Analytical, diagnostic and therapeutic context of Cxcl13


  1. Aberrant B1 cell migration into the thymus results in activation of CD4 T cells through its potent antigen-presenting activity in the development of murine lupus. Sato, T., Ishikawa, S., Akadegawa, K., Ito, T., Yurino, H., Kitabatake, M., Yoneyama, H., Matsushima, K. Eur. J. Immunol. (2004) [Pubmed]
  2. Intracerebral expression of CXCL13 and BAFF is accompanied by formation of lymphoid follicle-like structures in the meninges of mice with relapsing experimental autoimmune encephalomyelitis. Magliozzi, R., Columba-Cabezas, S., Serafini, B., Aloisi, F. J. Neuroimmunol. (2004) [Pubmed]
  3. CXC chemokine ligand 13 plays a role in experimental autoimmune encephalomyelitis. Bagaeva, L.V., Rao, P., Powers, J.M., Segal, B.M. J. Immunol. (2006) [Pubmed]
  4. 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]
  5. A B-cell-homing chemokine made in lymphoid follicles activates Burkitt's lymphoma receptor-1. Gunn, M.D., Ngo, V.N., Ansel, K.M., Ekland, E.H., Cyster, J.G., Williams, L.T. Nature (1998) [Pubmed]
  6. FDC-specific functions of p55TNFR and IKK2 in the development of FDC networks and of antibody responses. Victoratos, P., Lagnel, J., Tzima, S., Alimzhanov, M.B., Rajewsky, K., Pasparakis, M., Kollias, G. Immunity (2006) [Pubmed]
  7. 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]
  8. TNF Receptor-Associated Factor 2-Dependent Canonical Pathway Is Crucial for the Development of Peyer's Patches. Piao, J.H., Yoshida, H., Yeh, W.C., Doi, T., Xue, X., Yagita, H., Okumura, K., Nakano, H. J. Immunol. (2007) [Pubmed]
  9. Aberrant high expression of B lymphocyte chemokine (BLC/CXCL13) by C11b+CD11c+ dendritic cells in murine lupus and preferential chemotaxis of B1 cells towards BLC. Ishikawa, S., Sato, T., Abe, M., Nagai, S., Onai, N., Yoneyama, H., Zhang , Y., Suzuki, T., Hashimoto , S., Shirai, T., Lipp, M., Matsushima, K. J. Exp. Med. (2001) [Pubmed]
  10. CXCL13 is an arrest chemokine for B cells in high endothelial venules. Kanemitsu, N., Ebisuno, Y., Tanaka, T., Otani, K., Hayasaka, H., Kaisho, T., Akira, S., Katagiri, K., Kinashi, T., Fujita, N., Tsuruo, T., Miyasaka, M. Blood (2005) [Pubmed]
  11. The Rap GTPases mediate CXCL13- and sphingosine1-phosphate-induced chemotaxis, adhesion, and Pyk2 tyrosine phosphorylation in B lymphocytes. Durand, C.A., Westendorf, J., Tse, K.W., Gold, M.R. Eur. J. Immunol. (2006) [Pubmed]
  12. Role of CXC chemokine ligand 13, CC chemokine ligand (CCL) 19, and CCL21 in the organization and function of nasal-associated lymphoid tissue. Rangel-Moreno, J., Moyron-Quiroz, J., Kusser, K., Hartson, L., Nakano, H., Randall, T.D. J. Immunol. (2005) [Pubmed]
  13. Selectin ligand-independent priming and maintenance of T cell immunity during airborne tuberculosis. Schreiber, T., Ehlers, S., Aly, S., Hölscher, A., Hartmann, S., Lipp, M., Lowe, J.B., Hölscher, C. J. Immunol. (2006) [Pubmed]
  14. Cutting edge: the B cell chemokine CXC chemokine ligand 13/B lymphocyte chemoattractant is expressed in the high endothelial venules of lymph nodes and Peyer's patches and affects B cell trafficking across high endothelial venules. Ebisuno, Y., Tanaka, T., Kanemitsu, N., Kanda, H., Yamaguchi, K., Kaisho, T., Akira, S., Miyasaka, M. J. Immunol. (2003) [Pubmed]
  15. CXCL13 is required for B1 cell homing, natural antibody production, and body cavity immunity. Ansel, K.M., Harris, R.B., Cyster, J.G. Immunity (2002) [Pubmed]
  16. Design, synthesis, and initial evaluation of high-affinity technetium bombesin analogues. Baidoo, K.E., Lin, K.S., Zhan, Y., Finley, P., Scheffel, U., Wagner, H.N. Bioconjug. Chem. (1998) [Pubmed]
  17. Specific antibody-forming B-lymphocyte colonies. I. Distribution and nature of SRBC antibody-forming B-lymphocyte colonies in mouse lyphomyeloid organs. Claësson, M.H., Layton, J.E., Luckenbach, G.A. Immunology (1978) [Pubmed]
  18. Increased circulating CD11b+CD11c+ dendritic cells (DC) in aged BWF1 mice which can be matured by TNF-alpha into BLC/CXCL13-producing DC. Ishikawa, S., Nagai, S., Sato, T., Akadegawa, K., Yoneyama, H., Zhang, Y.Y., Onai, N., Matsushima, K. Eur. J. Immunol. (2002) [Pubmed]
  19. Altered localization of CXCL13 expressing cells in mice deficient in Pactolus following an inflammatory stimulus. Hojgaard, A., Close, R., Dunn, D.M., Weiss, R.B., Weis, J.J., Weis, J.H. Immunology (2006) [Pubmed]
  20. BLC expression in pancreatic islets causes B cell recruitment and lymphotoxin-dependent lymphoid neogenesis. Luther, S.A., Lopez, T., Bai, W., Hanahan, D., Cyster, J.G. Immunity (2000) [Pubmed]
  21. Cutting edge: differential roles for phosphoinositide 3-kinases, p110gamma and p110delta, in lymphocyte chemotaxis and homing. Reif, K., Okkenhaug, K., Sasaki, T., Penninger, J.M., Vanhaesebroeck, B., Cyster, J.G. J. Immunol. (2004) [Pubmed]
  22. Abnormal organogenesis of Peyer's patches in mice deficient for NF-kappaB1, NF-kappaB2, and Bcl-3. Paxian, S., Merkle, H., Riemann, M., Wilda, M., Adler, G., Hameister, H., Liptay, S., Pfeffer, K., Schmid, R.M. Gastroenterology (2002) [Pubmed]
  23. In vivo-activated CD4 T cells upregulate CXC chemokine receptor 5 and reprogram their response to lymphoid chemokines. Ansel, K.M., McHeyzer-Williams, L.J., Ngo, V.N., McHeyzer-Williams, M.G., Cyster, J.G. J. Exp. Med. (1999) [Pubmed]
  24. 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]
  25. CXCL13 neutralization reduces the severity of collagen-induced arthritis. Zheng, B., Ozen, Z., Zhang, X., De Silva, S., Marinova, E., Guo, L., Wansley, D., Huston, D.P., West, M.R., Han, S. Arthritis Rheum. (2005) [Pubmed]
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