Altered expression of the receptor-ligand pair CXCR5/CXCL13 in B cells during chronic HIV-1 infection.
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/microL). 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.
Cagigi
Alberto
A
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Mowafi
Frida
F
Phuong Dang
Linh V
LV
Tenner-Racz
Klara
K
Atlas
Ann
A
Grutzmeier
Sven
S
Racz
Paul
P
Chiodi
Francesca
F
Nilsson
Anna
A
D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002478:Cells, Cultured; D054382:Chemokine CXCL13 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D015658:HIV Infections / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D054380:Receptors, CXCR5 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
D000954:Antigens, Surface; C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; D054382:Chemokine CXCL13; D054380:Receptors, CXCR5