Natural Killer Cell Regulation of B Cell Responses in the Context of Viral Infection

Secretion of both neutralizing and nonneutralizing virus-specific antibodies by B cells is a key component of immune control of many virus infections and a critical benchmark of successful preventative vaccines. Natural killer (NK) cells also play a vital role in antiviral immune defense via cytolytic elimination of infected cells and production of proinflammatory antiviral cytokines. Accumulating evidence points to multifaceted crosstalk between NK cells and antiviral B cell responses that can determine virus elimination, pathogenesis of infection, and efficacy of vaccine-elicited protection. These outcomes are a result of both positive and negative influences of NK cells on the B cell responses, as well as canonical antiviral killing of infected B cells. On one hand, NK cell-derived cytokines such as interferon-gamma (IFN-gamma) may promote B cell activation and enhance immunoglobulin production. In contrast, NK cell immunoregulatory killing of CD4 T cells can limit affinity maturation in germinal centers resulting in weak infection or vaccine induction of antiviral neutralizing antibodies. In this review, we will discuss these and other dueling contributions of NK cells to B cell responses during virus infection or vaccination.