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

• Published in: Blood Vol. 112; no. 12; pp. 4401 - 4410
• Main Authors: Cagigi, Alberto, Mowafi, Frida, Phuong Dang, Linh V., Tenner-Racz, Klara, Atlas, Ann, Grutzmeier, Sven, Racz, Paul, Chiodi, Francesca, Nilsson, Anna
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01-12-2008; Americain Society of Hematology
• Subjects: Adult; Aged; Antigens, Surface - genetics; Antigens, Surface - metabolism; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Biological and medical sciences; 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; Human viral diseases; Humans; Infectious diseases; Male; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Oligonucleotide Array Sequence Analysis; Receptors, CXCR5 - genetics; Receptors, CXCR5 - metabolism; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Young Adult; Human; Immunopathology; HIV-1 virus; Ligand; Pathogenesis; Cytokine; Retroviridae; AIDS; CXCL13 chemokine; B-Lymphocyte; Gene expression; Immune deficiency; Lentivirus; Infection; Virus; Viral disease; CXCR5 chemokine receptor; Human immunodeficiency virus
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2008-02-140426

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.