Immunological tolerance as a barrier to protective HIV humoral immunity

• Published in: Current opinion in immunology Vol. 47; pp. 26 - 34
• Main Authors: Schroeder, Kristin MS, Agazio, Amanda, Torres, Raul M
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2017
• Subjects: AIDS Vaccines - immunology; Animals; Antibodies, Neutralizing - immunology; Autoantibodies - genetics; Autoantibodies - metabolism; B-Lymphocytes - physiology; Disease Models, Animal; HIV Antibodies - immunology; HIV Infections - immunology; HIV-1 - physiology; Humans; Immune Evasion; Immune Tolerance; Immunity, Humoral; Mice; Mice, Transgenic
• ISSN: 0952-7915; 1879-0372
• DOI: 10.1016/j.coi.2017.06.004

[Display omitted] •bnAbs isolated from HIV infected individuals display autoreactive specificities.•B cell development in HIV-1 bnAb Ig knockin mice is limited by central tolerance.•Autoimmune individuals and autoimmune-prone mouse strains produce HIV-1 bnAbs.•If a transient breach in tolerance would be helpful to develop bnAbs is not known.•How peripheral tolerance/B cell anergy limits the HIV response is not fully understood. HIV-1 infection typically eludes antibody control by our immune system and is not yet prevented by a vaccine. While many viral features contribute to this immune evasion, broadly neutralizing antibodies (bnAbs) against HIV-1 are often autoreactive and it has been suggested that immunological tolerance may restrict a neutralizing antibody response. Indeed, recent Ig knockin mouse studies have shown that bnAb-expressing B cells are largely censored by central tolerance in the bone marrow. However, the contribution of peripheral tolerance in limiting the HIV antibody response by anergic and potentially protective B cells is poorly understood. Studies using mouse models to elucidate how anergic B cells are regulated and can be recruited into HIV-specific neutralizing antibody responses may provide insight into the development of a protective HIV-1 vaccine.