Expression of CXCL12 receptors in B cells from Mexican Mestizos patients with systemic Lupus erythematosus

J Transl Med. 2012 Dec 18;10:251. doi: 10.1186/1479-5876-10-251.

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.

Result: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Cell Count
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Chemokine CXCL12 / pharmacology
  • Chemotaxis / drug effects
  • Demography
  • Ethnic Groups*
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / metabolism*
  • Lupus Erythematosus, Systemic / pathology*
  • Male
  • Mexico
  • Middle Aged
  • Plasma Cells / drug effects
  • Plasma Cells / metabolism
  • Plasma Cells / pathology
  • Receptors, CXCR / genetics
  • Receptors, CXCR / metabolism*
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism*
  • Young Adult

Substances

  • ACKR3 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Receptors, CXCR
  • Receptors, CXCR4