title: Expression of CXCL12 receptors in B cells from Mexican Mestizos patients with systemic Lupus erythematosus.
abstract: BACKGROUND
  Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by B-cell hyper-reactivity and the production of pathogenic anti-nuclear-directed auto-antibodies (Abs). B-cell ontogeny is partly dependent on the CXCL12/CXCR4 axis for which the contribution to SLE pathogenesis remains unclear. CXCR7, the novel receptor for CXCL12, is differentially expressed among memory B-cell subsets. However, its biological role in SLE remains to be explored.
  
  
  METHODS
  Relative CXCR4 and CXCR7 expression levels were compared by quantitative PCR in leukocytes from blood samples of 41 Mexican Mestizos patients with SLE and 45 ethnicity-matched healthy subjects. Intracellular and membrane expression of both receptors was analyzed by flow cytometry in naive and Ab-secreting B cells. B-cell responsiveness to CXCL12 was investigated using Transwell-based chemotaxis assays. Data were analyzed using the Kruskal-Wallis test for comparisons of values amongst healthy controls and patients with inactive or active SLE, and non-parametrically using the Mann-Whitney U-test for multiple comparisons and unpaired samples. Correlations were determined by Spearman's ranking.
  
  
  RESULTS
  SLE leukocytes displayed reduced levels of CXCR4 and CXCR7 transcripts. In SLE patients, a significant defect in CXCR4 expression was detected at the surface of naive and Ab-secreting B cells, associated with an abnormal intracellular localization of the receptor. CXCR7 predominantly localized in cytosolic compartments of B cells from healthy and SLE individuals. Disease activity did not impact on these expression patterns. Altered receptor compartmentalization correlated with an impaired CXCL12-promoted migration of SLE B cells.
  
  
  CONCLUSIONS
  Our data highlight a down-regulation of CXCL12 receptors on circulating B cells from SLE patients that likely influences their migratory behavior and distribution.
authors.affiliation: Université Paris-Sud, Laboratoire "Cytokines, Chimiokines et Immunopathologie", UMR_S996, Clamart, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Biajoux
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bignon
authors.forename: Christelle
authors.initials: C
authors.lastname: Freitas
authors.forename: Valérie
authors.initials: V
authors.lastname: Martinez
authors.forename: Marcus
authors.initials: M
authors.lastname: Thelen
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Lima
authors.forename: Juan
authors.initials: J
authors.lastname: Jakez-Ocampo
authors.forename: Dominique
authors.initials: D
authors.lastname: Emilie
authors.forename: Luis
authors.initials: L
authors.lastname: Llorente
authors.forename: Karl
authors.initials: K
authors.lastname: Balabanian
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D003710:Demography; D005006:Ethnicity; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008800:Mexico; D008875:Middle Aged; D010950:Plasma Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D054387:Receptors, CXCR / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: C501896:ACKR3 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D054387:Receptors, CXCR; D019718:Receptors, CXCR4