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Mucosal B cells and their function
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Jo Spencer, Edward N. Janoff, Per Brandtzaeg
Several chemokines contribute to lymphocyte trafficking and determinants of lymphocyte positioning in lymphoid tissue (Figure 10.7). The human B cell-attracting chemokine (BCA-1, CXCL13) is produced in human lymph node follicles. CXCL13 and its receptor CXCR5 are involved in the formation of organized lymphoid tissue by upregulating LTα1β2 on B cells, establishing a positive-feedback loop to generate follicle formation and attracting B cells into the tissue. The follicular expression of murine CXCL13 is reportedly stronger in murine Peyer's patches than in peripheral lymph nodes. Other chemokines acting on B cells include stromal cell-derived factor 1 (SDF-1, CXCL12), which is produced by cells lining tonsillar germinal centers and attracts naive and memory B cells that express CXCR4, at least in vitro.
Lymphocyte homing and immunology of extranodal lymphoid tissues
Published in Franco Cavalli, Harald Stein, Emanuele Zucca, Extranodal Lymphomas, 2008
Mariagrazia Uguccioni, James J Campbell, Katrin Kuscher, Marshall E Kadin
Many publications have shown CXCL13 and its selective receptor CXCR5, in different extranodal B-cell lymphomas, as the primary central nervous system lymphoma (PCNSL).99 PCNSL is a rare, but often rapidly fatal form of non-Hodgkin’s B-cell lymphomas which arises in the CNS, involves the brain, spinal cord, meninges, and/or eye, and has a low propensity to metastasize. Gene expression profiling, using cDNA microarrays for cytokines/chemokines and their receptors, has been utilized to assess the role of the dysregulation of the endogenous immune system in PCNSL, extranodal and nodal lymphomas. This study, although employing few cases of each subtype, has underlined the importance of CXCL13, in addition to the chemokines active on monocytes and T lymphocytes.100 CXCL13, a B-cell-attracting chemokine, has been the first chemokine identified in malignant B lymphocytes of PCNSL.99 The protein, but not its mRNA, has been detected also on vascular endothelium, within the tumor mass. It has been hypothesized that there is an active mechanism of transport from the source to endothelial cells. Indeed, an active transport from the stroma to endothelial cells has been reported for other chemokines.101 In addition, malignant B cells express CXCR5, the selective CXCL13 receptor.99 This latter feature suggests a role for CXCL13 in the pathogenesis of PCNSL. Recent publications report that malignant B lymphocytes in PCNSL express CXCL12, as well as its selective receptor CXCR4.102–104 These data need confirmation at the mRNA level, but corroborate the need for thoughtful studies to assess the role of chemokines in PCNSL development and localization.
Altered Expression of CXCL13 and Its Chemokine Receptor CXCR5 on B Lymphocytes during Active Graves’ Orbitopathy
Published in Current Eye Research, 2021
Shangtao Wan, Miaoli Lin, Yuxiang Mao, Xiaoqing Chen, Dan Liang
The dynamics of lymphocyte entry into peripheral and lymphoid tissues are partially regulated by chemokine receptors on lymphocytes and their respective ligands (chemokines) expressed in different tissue compartments.9 B cell-attracting chemokine 1 (BCA-1), also known as chemokine CXC ligand 13 (CXCL13), is essential for B-cell trafficking and homing by binding to its receptor CXC receptor type 5 (CXCR5), expressed on nearly all mature recirculating B cells.10 CXCL13 is generally secreted by stromal cells in B-cell areas of secondary lymphoid tissues (follicles) and is responsible for the recruitment of CXCR5+ B cells to form a germinal center.11,12 Interestingly, CXCL13 is also capable of inducing the ectopic lymphoid-like tissues (lymphoid neogenesis), which are frequently observed in autoimmune diseases and chronic inflammatory processes. Aberrant CXCL13/CXCR5 activation has been implicated in autoimmune thyroid disease, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjögren’s syndrome (pSS), myasthenia gravis, and multiple sclerosis.13–16 The elevated production of CXCL13 has been correlated with the activity of RA and SLE.17,18
The potential for CXCL13 in CSF as a differential diagnostic tool in central nervous system infection
Published in Expert Review of Anti-infective Therapy, 2020
Ilias Masouris, Matthias Klein, Uwe Ködel
Chemokines are chemotactic cytokines that orchestrate immune cell migration and positioning at organ level in homeostasis, in acute inflammation, and during the generation and regulation of adoptive immune responses [6]. To date, more than 40 chemokines have been identified in humans, which can be grouped into four different classes depending on the positioning of their N-terminal cysteine residues, namely into CC, CXC, XC, and CX3C chemokines. Chemokines mediate their activity through binding to their cognate seven transmembrane-spanning G protein-coupled receptors, thereby forming so-called chemokine ligand/receptor pair axes [7]. During last years, chemokines have been implicated as key regulatory factors in inflammatory CNS disorders [8–11], raising the question if any of them could serve as diagnostic, therapeutic and/or prognostic markers in CNS infectious. In the last 20 years, one chemokine of the CXC-family, CXCL13, has emerged as a key component in certain inflammatory disorders. In this review, we provide a comprehensive perspective of the potential role of CXCL13 as a differential diagnostic tool in various CNS infections, concentrating on neuroborreliosis and neurosyphilis as the diseases with the most studies published on this topic so far.
The B-lymphocyte chemokine CXCL13 in the cerebrospinal fluid of children with Lyme neuroborreliosis: associations with clinical and laboratory variables
Published in Infectious Diseases, 2019
Bjørn Barstad, Dag Tveitnes, Ingvild Dalen, Sølvi Noraas, Ingvild S. Ask, Franziskus J. Bosse, Knut Øymar
This study has shown that the CXCL13 release in CSF during LNB infection in children is pronounced and present in the early phase of the disease. High levels of CXCL13 are associated with high levels of WBC and protein and detection of Borrelia antibodies in the CSF. We could not identify any demographic or clinical variables associated with the level of CXCL13 in children with LNB. Thus, CXCL13 is associated with LNB but probably not with specific features of the disease or duration of symptoms, supporting the role as a good diagnostic marker for LNB.