CpG Oligonucleotides Enhance Proliferative and Effector Responses of B Cells in HIV-Infected Individuals

• Published in: The Journal of immunology (1950) Vol. 181; no. 2; pp. 1199 - 1206
• Main Authors: Malaspina, Angela, Moir, Susan, DiPoto, Angela C, Ho, Jason, Wang, Wei, Roby, Gregg, O'Shea, Marie A, Fauci, Anthony S
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.07.2008
• Subjects: Adjuvants, Immunologic; B-Lymphocytes - immunology; Cell Proliferation; Cells, Cultured; Cytokines - immunology; Cytokines - metabolism; HIV; HIV Infections - immunology; HIV Infections - virology; Human immunodeficiency virus; Humans; Immunoglobulin G - immunology; Immunoglobulin G - metabolism; Lymphocyte Activation; Oligodeoxyribonucleotides - immunology; Toll-Like Receptor 9 - agonists; Toll-Like Receptor 9 - immunology; Toll-Like Receptor 9 - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.181.2.1199

Stimulation through TLR represents a new therapeutic approach for enhancing Ab responses to vaccination. Considering that Ab responses are decreased in HIV disease and that B cells express TLR9 and respond to TLR9 agonists, we investigated the responsiveness of B cell subpopulations from HIV-infected and uninfected individuals to the TLR9 agonist CpG oligonucleotide type B (CpG-B) in the presence and absence of BCR ligation and T cell help (CD40L). CpG-B was equally effective in stimulating the proliferation of naive B cells of HIV-infected individuals and HIV-negative individuals, and, when combined with BCR and CD40 ligation, cytokine secretion by naive B cells was also comparable in HIV-infected and uninfected individuals. In contrast, CD27(+) memory/activated B cells of HIV-infected individuals with active disease were less responsive to CpG-B in terms of proliferation and cytokine secretion when compared with CD27(+) B cells of HIV-negative and HIV-infected individuals whose viremia was controlled by antiretroviral therapy. These findings suggest that despite abnormalities in memory B cells of HIV-infected individuals with active disease, naive B cells of HIV-infected individuals, irrespective of disease status, can respond to TLR9 agonists and that the incorporation of such agents in vaccine formulations may enhance their Ab responses to vaccination.