| First Author | Schroeder KMS | Year | 2017 |
| Journal | J Exp Med | Volume | 214 |
| Issue | 8 | Pages | 2283-2302 |
| PubMed ID | 28698284 | Mgi Jnum | J:243972 |
| Mgi Id | MGI:5912751 | Doi | 10.1084/jem.20161190 |
| Citation | Schroeder KMS, et al. (2017) Breaching peripheral tolerance promotes the production of HIV-1-neutralizing antibodies. J Exp Med 214(8):2283-2302 |
| abstractText | A subset of characterized HIV-1 broadly neutralizing antibodies (bnAbs) are polyreactive with additional specificities for self-antigens and it has been proposed immunological tolerance may present a barrier to their participation in protective humoral immunity. We address this hypothesis by immunizing autoimmune-prone mice with HIV-1 Envelope (Env) and characterizing the primary antibody response for HIV-1 neutralization. We find autoimmune mice generate neutralizing antibody responses to tier 2 HIV-1 strains with alum treatment alone in the absence of Env. Importantly, experimentally breaching immunological tolerance in wild-type mice also leads to the production of tier 2 HIV-1-neutralizing antibodies, which increase in breadth and potency following Env immunization. In both genetically prone and experimentally induced mouse models of autoimmunity, increased serum levels of IgM anti-histone H2A autoantibodies significantly correlated with tier 2 HIV-1 neutralization, and anti-H2A antibody clones were found to neutralize HIV-1. These data demonstrate that breaching peripheral tolerance permits a cross-reactive HIV-1 autoantibody response able to neutralize HIV-1. |
