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Blood, 1 December 2008, Vol. 112, No. 12, pp. 4401-4410. Prepublished online as a Blood First Edition Paper on September 9, 2008; DOI 10.1182/blood-2008-02-140426.
Submitted February 19, 2008
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden * Corresponding author; email: anna.nilsson.1{at}ki.se.
HIV-1 infection is associated with B-cell abnormalities such as hypergammaglobulinemia, poor immunisation responses and loss of serological 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 CXCR4, CXCR5 and CCR7 receptors 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<0.05), a phenomenon associated with a low CD4 T-cell count (<350 cells/µ). Interestingly, an increased expression of CXCL13, the ligand for CXCR5, was found in peripheral B-cells from HIV-1 infected patients. Moreover upon B-cell activation in vitro, CXCL13 was secreted in culture. In addition, CXCL13 positive B-cells were also found in the lymph nodes of HIV-1 infected patients, but not in control tissue. B-cell migration towards CXCL13, CXCL12 and CCL21, ligands for CXCR5, CXCR4 and CCR7, was also evaluated. In patients with a low CD4 T-cell count, migration towards 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.
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