The chemokine CXCL13 is a key regulator of B cell recruitment to the cerebrospinal fluid in acute Lyme neuroborreliosis
Open Access
- 1 January 2009
- journal article
- Published by Springer Science and Business Media LLC in Journal of Neuroinflammation
- Vol. 6 (1), 42
- https://doi.org/10.1186/1742-2094-6-42
Abstract
The chemokine CXCL13 is known to dictate homing and motility of B cells in lymphoid tissue and has been implicated in the formation of ectopic lymphoid tissue in chronic inflammation. Whether it influences B cell trafficking during acute infection, is largely unclear. In previous studies, we showed that (I) CXCL13 levels are markedly increased in the B cell-rich cerebrospinal fluid (CSF) of patients with acute Lyme neuroborreliosis (LNB), and (II) CXCL13 is released by monocytes upon recognition of borrelial outer surface proteins by Toll-like receptor 2. Here, we assessed the role of CXCL13--in comparison to other chemokines--in the recruitment of B cells to the CSF of patients with acute LNB. Measurement of chemokines was done by ELISA. B cells were isolated from whole blood using magnetic cell separation (MACS). For migration experiments, a modified Boyden chamber assay was used and the migrated B cells were further analysed by FACS. The migration was inhibited either by preincubation of the CSF samples with neutralizing antibodies, heating to 60 degrees C, removal of proteins >3 kDa, or by pre-treatment of the B cells with pertussis toxin. The principal statistical tests used were one-way analysis of variance and Bonferroni test (chemokine measurements) as well as paired Student's t-test (migration experiments). Measurements of chemokine levels revealed an increase in three of the four known major B cell chemoattractants CXCL13, CCL19 and CXCL12 in LNB CSF. The CXCL13 CSF:serum ratio, as a measure of the chemotactic gradient, was substantially higher than that of CCL19 and CXCL12. Moreover, the chemotactic activity of LNB CSF was reduced up to 56% after preincubation with a neutralizing CXCL13 antibody, while combined preincubation with antibodies against CXCL13, CCL19, and CXCL12 did not lead to further reduction. Since treatment with pertussis toxin, heating to 60 degrees C, and removal of proteins >3 kDa abrogated the chemotactic activity, further not yet identified chemokines seem to be involved in B cell recruitment to LNB CSF. Combined, our study suggests a key role of CXCL13 in B cell migration to sites of infection as shown here for the CSF of LNB patients.This publication has 35 references indexed in Scilit:
- Helicobacter pylori and Antrum Erosion‐Specific Gene Expression Patterns: The Discriminative Role of CXCL13 and VCAM1 TranscriptsHelicobacter, 2008
- Mycobacterium tuberculosisTriggers Formation of Lymphoid Structure in Murine LungsThe Journal of Infectious Diseases, 2007
- Role of dendritic cell-derived CXCL13 in the pathogenesis of Bartonella henselae B-rich granulomaBlood, 2006
- Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitmentBrain, 2005
- The chemokine CXCL13 (BLC): A putative diagnostic marker for neuroborreliosisNeurology, 2005
- Overlapping Roles of CXCL13, Interleukin 7 Receptor α, and CCR7 Ligands in Lymph Node DevelopmentThe Journal of Experimental Medicine, 2003
- Ectopic Germinal Center Formation in Rheumatoid SynovitisAnnals of the New York Academy of Sciences, 2003
- Follicular stromal cells and lymphocyte homing to folliclesImmunological Reviews, 2000
- A chemokine-driven positive feedback loop organizes lymphoid folliclesNature, 2000
- B Cell–attracting Chemokine 1, a Human CXC Chemokine Expressed in Lymphoid Tissues, Selectively Attracts B Lymphocytes via BLR1/CXCR5The Journal of Experimental Medicine, 1998