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

A Cagigi, F Mowafi, LV Phuong Dang… - Blood, The Journal …, 2008 - ashpublications.org
A Cagigi, F Mowafi, LV Phuong Dang, K Tenner-Racz, A Atlas, S Grutzmeier, P Racz…
Blood, The Journal of the American Society of Hematology, 2008ashpublications.org
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 …
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/μL). 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.
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