B-Cell Development and Differentiation During HIV Infection: Tolerance Versus Immunity

ABSTRACT

Early after HIV infection, B-cell homeostasis is disrupted which results in autoantibody production and autoimmunity. The systemic inflammation induced during chronic HIV infection relaxes B-cell tolerance mechanisms that normally suppress this autoimmune pathology. Tolerance to self antigens is established during the development of B cells; however, rare, broadly neutralizing antibodies to HIV cross-react with host cellular antigens, suggesting that mechanisms of B-cell tolerance limit protective humoral responses to HIV. The association between HIV infection, induction of autoantibody and the emergence of neutralizing antibodies directed at HIV suggests that protective humoral immune responses may only occur after B-cell tolerance control mechanisms are relaxed.

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