High expression levels of B lymphocyte stimulator (BLyS) by dendritic cells correlate with HIV-related B-cell disease progression in humans

• Published in: Blood Vol. 117; no. 1; pp. 145 - 155
• Main Authors: Fontaine, Julie, Chagnon-Choquet, Josiane, Valcke, Han Sang, Poudrier, Johanne, Roger, Michel
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 06-01-2011; Americain Society of Hematology
• Subjects: Adult; APRIL protein; B-Cell Activating Factor - metabolism; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Biological and medical sciences; Cohort Studies; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - pathology; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Hematologic and hematopoietic diseases; HIV Infections - metabolism; HIV Infections - pathology; HIV Infections - virology; HIV-1 - pathogenicity; Human immunodeficiency virus; Human viral diseases; Humans; Infectious diseases; Interleukin-10 - metabolism; Interleukin-6 - metabolism; Male; Medical sciences; Tumor Necrosis Factor Ligand Superfamily Member 13 - metabolism; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Infection; Human; Immunopathology; Dendritic cell; Hematology; Antigen presenting cell; Viral disease; B cell activating factor; AIDS; B-Lymphocyte; Immune deficiency
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2010-08-301887

In view of assessing the possible contribution of dendritic cells (DCs) to HIV-related B-cell disorders, we have longitudinally measured B lymphocyte stimulator (BLyS) surface expression by myeloid DCs (mDCs) and concentrations of B-cell growth factors in the blood of subjects undergoing primary HIV infection with different rates of disease progression. We report that BLyS surface expression by mature mDCs and precursors as well as blood levels of BLyS, a proliferation-inducing ligand (APRIL), interleukin-6 (IL-6), and IL-10 increased above normal levels in both rapid and normal HIV progressors as quickly as in the acute phase of infection and persisting throughout the course of disease despite successful therapy. Consequently, hyperglobulinemia and high blood levels of circulating activated mature B cells and precursor/activated marginal zone (MZ)–like B cells were found throughout follow-up for both rapid and normal progressors. In contrast, mDC cell-surface expression of BLyS as well as blood levels of BLyS, immunoglobulin, activated mature B cells, and precursor/activated MZ-like B cells in aviremic slow progressors were similar to those observed in healthy donors. Interestingly, the levels of mature MZ B cells were significantly reduced in slow progressors. Our results suggest that DCs might modulate the outcome of the HIV-related B-cell disease progression through the expression of BLyS.