Viral subversion of B cell responses within secondary lymphoid organs

Key Points An efficient antibody response to an infecting virus requires the dynamic localization of B cells in unique niches and interaction with neighbouring cells and the local microenvironment. The long relationship between viruses and hosts has resulted in the evolution of several diverse viral strategies that interfere with B cell responses. Virus-induced type I interferon has emerged as a major player that inhibits antiviral humoral immune responses at multiple levels: first, it induces the lymph node recruitment of inflammatory monocytes that inhibit antiviral B cells; second, it promotes the expansion and differentiation of cytotoxic T lymphocytes that kill antiviral B cells; and third, it indirectly supports the differentiation of antiviral B cells into short-lived plasma cells. Further identification of the cellular and molecular mechanisms used by viruses to evade immune control might lead to new treatments for the termination of chronic viral infections and instruct the design of novel, rational vaccines. The development of multiphoton intravital microscopy has enabled detailed studies of humoral responses within lymphoid tissues. Here, Kuka and Iannacone cover recent studies of the viral subversion of B cell responses and discuss how these findings relate to our understanding of B cell activation within secondary lymphoid organs. Antibodies play a crucial role in virus control. The production of antibodies requires virus-specific B cells to encounter viral antigens in lymph nodes, become activated, interact with different immune cells, proliferate and enter specific differentiation programmes. Each step occurs in distinct lymph node niches, requiring a coordinated migration of B cells between different subcompartments. The development of multiphoton intravital microscopy has enabled researchers to begin to elucidate the precise cellular and molecular events by which lymph nodes coordinate humoral responses. This Review discusses recent studies that clarify how viruses interfere with antibody responses, highlighting how these mechanisms relate to our topological and temporal understanding of B cell activation within secondary lymphoid organs.