IL-10-producing B cells are induced early in HIV-1 infection and suppress HIV-1-specific T cell responses.

• Main Authors: Jun Liu, Wei Zhan, Connie J Kim, Kiera Clayton, Hanqi Zhao, Erika Lee, Jin Chao Cao, Blake Ziegler, Alexander Gregor, Feng Yun Yue, Sanja Huibner, Sonya MacParland, Jordan Schwartz, Hai Han Song, Erika Benko, Gabor Gyenes, Colin Kovacs, Rupert Kaul, Mario Ostrowski
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2014-01-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC3931714?pdf=render

A rare subset of IL-10-producing B cells, named regulatory B cells (Bregs), suppresses adaptive immune responses and inflammation in mice. In this study, we examined the role of IL-10-producing B cells in HIV-1 infection. Compared to uninfected controls, IL-10-producing B cell frequencies were elevated in both blood and sigmoid colon during the early and chronic phase of untreated HIV-1 infection. Ex vivo IL-10-producing B cell frequency in early HIV-1 infection directly correlated with viral load. IL-10-producing B cells from HIV-1 infected individuals were enriched in CD19(+)TIM-1(+) B cells and were enriched for specificity to trimeric HIV-1 envelope protein. Anti-retroviral therapy was associated with reduced IL-10-producing B cell frequencies. Treatment of B cells from healthy donors with microbial metabolites and Toll-like receptor (TLR) agonists could induce an IL-10 producing phenotype, suggesting that the elevated bacterial translocation characteristic of HIV-1 infection may promote IL-10-producing B cell development. Similar to regulatory B cells found in mice, IL-10-producing B cells from HIV-1-infected individuals suppressed HIV-1-specific T cell responses in vitro, and this suppression is IL-10-dependent. Also, ex vivo IL-10-producing B cell frequency inversely correlated with contemporaneous ex vivo HIV-1-specific T cell responses. Our findings show that IL-10-producing B cells are induced early in HIV-1 infection, can be HIV-1 specific, and are able to inhibit effective anti-HIV-1 T cell responses. HIV-1 may dysregulate B cells toward Bregs as an immune evasion strategy.