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

• These results underscore a crucial role for the TNFR1-TRAF2-RelA-dependent canonical pathway in the development of PP through up-regulation of cxcl13 mRNA [8].
• 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 [9].
• Thus, aberrant high expression of BLC by myeloid dendritic cells in the target organs in aged BWF1 mice may play a pivotal role in breaking immune tolerance in the thymus and in recruiting autoantibody-producing B cells in the development of murine lupus [9].
• In addition, CXCL13 induced B-cell adhesion to mucosal addressin cell adhesion molecule 1 (MAdCAM-1) by activating alpha4 integrin [10].
• The Rap GTPases mediate CXCL13- and sphingosine1-phosphate-induced chemotaxis, adhesion, and Pyk2 tyrosine phosphorylation in B lymphocytes [11].

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

• We also show that the NALT of Cxcl13(-/-) and plt/plt mice exhibits some, but not all, of the structural and functional defects observed in the NALT of Ltalpha(-/-) mice [12].
• BLC expression in pancreatic islets causes B cell recruitment and lymphotoxin-dependent lymphoid neogenesis [20].
• In addition to attracting B cells, BLC expression led to development of lymph node-like structures that contained B and T cell zones, high endothelial venules, stromal cells, and the chemokine SLC [20].
• B cells deficient in p110delta showed diminished chemotactic responses, especially to CXCL13 [21].
• Expression of the chemokines macrophage inflammatory protein-3alpha, B-lymphocyte chemoattractant, and thymus-expressed chemokine is impaired in epithelial cells and in the subendothelial dome area that is not well defined [22].

Analytical, diagnostic and therapeutic context of Cxcl13

• In situ hybridization of secondary follicles for BLC showed high expression in mantle zones and low expression in germinal centers [23].
• 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) [24].
• By reverse transcription-polymerase chain reaction (RT-PCR), we find that gene expression of CXCL13, a chemokine involved in B-cell recruitment into lymphoid follicles, and BAFF, a key regulator of B-cell survival, is markedly and persistently upregulated in the CNS of mice with relapsing-remitting and chronic-relapsing EAE [2].
• CXCL13 is produced by cells in the omentum and by peritoneal macrophages, and in adoptive transfers, B1 cells home to the omentum and the peritoneal cavity in a CXCL13-dependent manner [15].
• CXCL13 neutralization reduces the severity of collagen-induced arthritis [25].

References