IL-10-Producing B Cells Are Induced Early in HIV-1 Infection and Suppress HIV-1-Specific T Cell Responses

Abstract

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.

CD4+ T Cell–Derived IL-21 and Deprivation of CD40 Signaling Favor the In Vivo Development of Granzyme B–Expressing Regulatory B Cells in HIV Patients

“…Therefore, it is not surprising that the phenotype of GraB cells (enhanced expression of GrB, IDO, CD5, CD10, CD43, CD86, and CD147) is only compatible, in part, with the various regulatory B cell phenotypes described elsewhere. Of note, a recent publication described a minor population of IL-10 + B cells in untreated HIV patients (38). In contrast, in the current study, we did not detect a significant difference in IL-10 expression between healthy B cells and GraB cells from HIV patients, and we found that T cell regulation by GraB cells occurred in an IL-10-independent manner (data no shown).…”

The N-N non-covalent domain of the nucleocapsid protein of type 2 porcine reproductive and respiratory syndrome virus enhances induction of IL-10 expression

“…Increased IL-10 expression has been reported to be a strategy of several viral pathogens, such as HIV-1, rhinovirus and cytomegalovirus, to suppress host immune responses (Koponen et al, 2013;Liu et al, 2014;Loebbermann et al, 2012;Mason et al, 2013;Redpath et al, 2001). Upregulation of IL-10 could lead to the suppression of antigen-presenting-cell functions, including the production of pro-inflammatory cytokines (Redpath et al, 2001).…”

Human regulatory B cells in health and disease: therapeutic potential

“…Multiple subsets of B cells that produce IL-10, often with overlapping surface markers but diverse functions, have been reported and are collectively referred to as Bregs (12 + B cells, which have all been shown to suppress proinflammatory responses (4,(13)(14)(15)(16). Notably, fewer than 20% of the B cells within these different B cell subsets produce IL-10 and suppress immune responses.…”