Altered expression of the receptor-ligand pair CXCR5/CXCL13 in B cells during chronic HIV-1 infection

Blood. 2008 Dec 1;112(12):4401-10. doi: 10.1182/blood-2008-02-140426. Epub 2008 Sep 9.

Abstract

HIV-1 infection is associated with B-cell abnormalities, such as hypergammaglobulinemia, poor immunization responses, and loss of serologic memory. To determine whether altered expression of chemokine receptors and their ligands may play a role in B-cell dysfunctions during HIV-1 infection, the expression of CXC chemokine receptor 4 (CXCR4), CXCR5, and CC chemokine receptor 7 (CCR7) and their respective ligands on CD19(+) B cells were examined in HIV-1-infected patients and controls. We report a decreased CXCR5 expression on B cells from patients (P < .05), a phenomenon associated with a low CD4 T-cell count (< 350 cells/microL). Interestingly, an increased expression of CXC chemokine ligand 13 (CXCL13), the ligand for CXCR5, was found in peripheral B cells from HIV-1-infected patients. Moreover, on B-cell activation in vitro, CXCL13 was secreted in culture. CXCL13(+) B cells were also found in the lymph nodes of HIV-1-infected patients, but not in control tissue. B-cell migration toward CXCL13, CXCL12, and CC chemokine ligand 21 (CCL21), ligands for CXCR5, CXCR4, and CCR7 was also evaluated. In patients with a low CD4 T-cell count, migration toward all ligands was increased. Our findings indicate that altered expression of the chemokine receptor-ligand pair, CXCR5/CXCL13, may participate in the establishment of B-cell dysfunctions during HIV-1 infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Case-Control Studies
  • Cells, Cultured
  • Chemokine CXCL13 / genetics
  • Chemokine CXCL13 / metabolism*
  • Chemokine CXCL13 / pharmacology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • HIV Infections / blood
  • HIV Infections / genetics
  • HIV Infections / immunology
  • HIV Infections / metabolism*
  • HIV-1*
  • Humans
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Receptors, CXCR5 / genetics
  • Receptors, CXCR5 / metabolism*
  • Young Adult

Substances

  • Antigens, Surface
  • CXCL13 protein, human
  • CXCR5 protein, human
  • Chemokine CXCL13
  • Receptors, CXCR5