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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.


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Submitted February 19, 2008
Accepted August 14, 2008

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

Alberto Cagigi, Frida Mowafi, Linh Vu Phuong Dang, Klara Tenner-Racz, Ann Atlas, Sven Grutzmeier, Paul Racz, Francesca Chiodi, and Anna Nilsson*

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
Department of Pathology and the Körber Laboratory for AIDS Research, Bernhard-Nocht Institute for Tropical Diseases, Hamburg, Germany
Department of Medicine Solna, Infectious Diseases Unit, Karolinska University Hospital, Stockholm, Sweden
Gay Men's Health Clinic, The Soder Hospital, Stockholm, Sweden
Department of Women and Child Health, 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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Proc. Natl. Acad. Sci. USAHome page
S. Pensieroso, A. Cagigi, P. Palma, A. Nilsson, C. Capponi, E. Freda, S. Bernardi, R. Thorstensson, F. Chiodi, and P. Rossi
From the Cover: Timing of HAART defines the integrity of memory B cells and the longevity of humoral responses in HIV-1 vertically-infected children
PNAS, May 12, 2009; 106(19): 7939 - 7944.
[Abstract] [Full Text] [PDF]



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