Journal
BLOOD
Volume 112, Issue 12, Pages 4401-4410Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-02-140426
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Funding
- Swedish Research Council (MRC)
- Swedish International Development Agency
- Regione Autonoma della Sardegna, Cagliari, Italy
- Istituto Italiano di Cultura C. M. Lerici Foundation, Stockholm, Sweden
- German Ministry of Education and Research
- Compentence Network for HIV/AIDS [FKZ 01KI0501]
- Stockholm County Council
- Karolinska Institutet
- EU
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HIV-1 infection is associated with B-cell abnormalities, such as hypergamma-globulinemia, 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/mu L). 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. (Blood. 2008;112:4401-4410)
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