CXCL13

Official Full Name

C-X-C motif chemokine ligand 13

Organism

Homo sapiens

GeneID

10563

Background

B lymphocyte chemoattractant, independently cloned and named Angie, is an antimicrobial peptide and CXC chemokine strongly expressed in the follicles of the spleen, lymph nodes, and Peyer's patches. It preferentially promotes the migration of B lymphocytes (compared to T cells and macrophages), apparently by stimulating calcium influx into, and chemotaxis of, cells expressing Burkitt's lymphoma receptor 1 (BLR-1). It may therefore function in the homing of B lymphocytes to follicles. [provided by RefSeq, Oct 2014]

Synonyms

BLC; BCA1; ANGIE; BCA-1; BLR1L; ANGIE2; SCYB13;

Bio Chemical Class

Cytokine: CXC chemokine

Protein Sequence

MKFISTSLLLMLLVSSLSPVQGVLEVYYTSLRCRCVQESSVFIPRRFIDRIQILPRGNGCPRKEIIVWKKNKSIVCVDPQAEWIQRMMEVLRKRSSSTLPVPVFKRKIP

Open

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Detailed Information

CXCL13 is a small chemokine with a molecular weight of 8-10 kDa, originally discovered as B-lymphocyte chemoattractant (BLC) or B-cell attracting chemokine 1 (BCA-1). It is part of the CXC chemokine group and helps B-lymphocytes move by causing them to change their position and increase calcium levels. It does not have a major effect on T lymphocytes, monocytes, or neutrophils. CXCR5, also called Burkitt's lymphoma receptor 1 (BLR1), is the only known receptor for CXCL13. It belongs to a group of receptors called G-protein coupled receptors, which are defined by having seven sections that pass through cell membranes. This pairing of a ligand and receptor helps control calcium movement inside cells and directs cell movement. It is important for maintaining balance in the immune system and for the growth of diseases.

Expression Distribution and Regulatory Mechanisms

CXCL13 is found in large amounts in secondary lymphoid organs like the spleen, lymph nodes, and Peyer's patches. Follicular dendritic cells produce most of the CXCL13 in lymphoid tissues. They are important for the B cell regions in busy tonsils and lymph nodes. Recent studies have also shown functional CXCL13 production in neurons and astrocytes in the peripheral and central nervous systems. In the tumor setting, follicular helper T cells (TFH) are the primary producers of CXCL13, which may help B cells find their location, develop, and mature. Tumor-associated fibroblasts, CD8+ T cells, and some cancer cells can produce CXCL13.

CXCL13 expression is influenced by a complex transcriptional regulatory network, with transcription factors p52/RelB from the NF-κB pathway playing critical roles in macrophages and B cells. Mice lacking p52 or RelB show defects in B cell follicle and germinal center formation. Notably, NF-κB proteins also serve as key transcription factors for the immune checkpoint PD-L1, suggesting that NF-κB may regulate both immune checkpoint blockade responses and T/B cell recruitment.

CXCR5 expression is controlled by different transcriptional mechanisms. In T cells, BCL6 activates CXCR5 expression by repressing inhibitory pathways. Transcription factor E2A activates CXCR5 expression by directly binding to its enhancer region, while Id2/Id3 inhibit CXCR5 expression by antagonizing E2A. BCL6 directly represses Id2 expression in T cells, thereby activating E2A and stimulating CXCR5 expression. Interestingly, there is a mutually exclusive and antagonistic relationship between BCL6 and Blimp-1. In this competition, dominance of Blimp-1 leads naive CD4+ T cells to differentiate into CXCR5-negative Th1 cells; conversely, activation of upstream transcription factor T cell factor 1 (TCF-1) leads naive CD4+ T cells to differentiate into CXCR5-expressing TFH cells.

Figure 1: The CXCL13-CXCR5 pathway triggers GPCR-mediated signaling that influences growth, invasion, and migration, while promoting chronic pain through proinflammatory cytokine release and neuron activation, with p38 MAPK enhancing neuronal excitability. Figure 1. The CXCL13-CXCR5 pathway promotes chronic pain via GPCR signaling, cytokine release, and neuronal excitability enhancement. (Zheng K, et al., 2024)

Signal Transduction Pathway

When CXCL13 attaches to CXCR5, it starts a series of reactions inside the cell that mainly involve two protein components called Gαq and Gαi2. In prostate cancer cells, research shows that Gα13 combines with CXCR5 when treated with CXCL13. In contrast, Gαq and Gαi2 are linked to CXCR5 without CXCL13 but separate when CXCL13 is present. When a ligand attaches to GPCRs, it helps swap GDP for GTP on small G proteins. This activates the G proteins, making them separate from the GPCR and starting additional signaling processes.

RNA interference experiments showed that siRNAs aimed at Gαq and Gαi2 greatly reduced the invasion of prostate cancer cells driven by CXCL13. This suggests that the CXCL13/CXCR5/Gαq signaling pathway is important for controlling cell movement. Researchers studied how two proteins, Rac and RhoA, work in cancer cells. They discovered that CXCL13 only activates Rac and not RhoA, and this process relies on proteins called Gαq and Gαi2.

In immune cells, Gαi2 is more critical. Studies show that Gαi2-deficient B cells poorly respond to CXCL13 treatment, failing to migrate toward chemokine sites in transwell assays. When transplanted into recipient mice, they cannot migrate to lymph nodes. Similarly, CD4+ and CD8+ T cells lacking Gαi2 exhibit significantly reduced migration capacity, averaging 4-7 times less than wild-type cells under chemotactic conditions. Immunohistochemical staining shows structural abnormalities in secondary lymphoid organs of Gαi2-deficient mice, including disrupted marginal zone T cell expression, germinal center formation failure, and reduced lymphoid tissue structures.

Physiological and Pathological Functions

Under physiological conditions, the CXCL13-CXCR5 axis maintains immune system function by regulating key processes like B cell homing to lymphoid tissues, participating in germinal center formation and maintenance, and coordinating adaptive immune responses. In CXCL13 or CXCR5-deficient mice, B cell localization is severely disrupted, leading to impaired immune functions.

Pathologically, particularly in tumor microenvironments, this signaling axis exhibits more complex regulation. CXCL13 can recruit CXCR5-positive B and T cells, promoting tertiary lymphoid structures (TLSs) formation, which are structurally and functionally similar to secondary lymphoid organs and often correlate with better prognoses. Tumor-associated fibroblasts secrete CXCL13 to recruit CXCR5+ B cells expressing lymphotoxin-α1β2, thus expanding TLSs in the tumor microenvironment. CD8+ T cells further induce TLS formation by mediating tumor-associated fibroblast organization.

In the context of immunotherapy, CXCL13 plays a crucial role. Studies have found that in head and neck, cervical, and ovarian cancers, exhausted CD4+ T cells (characterized by high PD-1 and CD39 expression) can secrete CXCL13 and express the transcription factor TOX. Similarly, in non-small cell lung cancer, PD-1-high CD8+ tumor-infiltrating T cells produce more CXCL13 than PD-1-negative counterparts, clustering within TLSs, predicting effective responses to anti-PD-1 treatment, and correlating positively with overall survival.

Additionally, unusual activity of the CXCL13-CXCR5 pathway is strongly associated with the growth and worsening of several types of cancer, such as breast, colorectal, lung, prostate, mouth, kidney, neuroblastoma, and lymphomas. In these cancers, the CXCL13/CXCR5 signaling helps tumors grow, spread, and move into other areas using complicated processes. In conditions affecting the brain and long-lasting pain, CXCL13 and CXCR5 play a role in how the immune system interacts with the nervous system and contributes to inflammation. This makes them promising targets for new treatment options.

References:

Hussain M, Liu J, et al. CXCL13 Signaling in the Tumor Microenvironment. Adv Exp Med Biol. 2021;1302:71-90.
Hsieh CH, Jian CZ, et al. Potential Role of CXCL13/CXCR5 Signaling in Immune Checkpoint Inhibitor Treatment in Cancer. Cancers (Basel). 2022 Jan 7;14(2):294.
Zheng K, Chen M, et al. Chemokine CXCL13-CXCR5 signaling in neuroinflammation and pathogenesis of chronic pain and neurological diseases. Cell Mol Biol Lett. 2024 Oct 29;29(1):134.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry