Abstract
Humoral immunity is a critical component of the coordinated response required to resolve viral infections and mediate protection following pathogen clearance or vaccination. A better understanding of factors shaping the memory B cell response will allow tailored development of efficient preventative vaccines against emerging acute viral infections, therapeutic vaccines, and immunotherapies for chronic viral infections. Here, we use recent data obtained by profiling antigen‐specific B cell responses in hepatitis B as a framework to explore lessons that can be learnt from different viral infections about the diverse influences on humoral immunity. Hepatitis B provides a paradigm where successful B cell responses in resolved or vaccinated individuals can be contrasted to the failed response in chronic infection, while also exemplifying the degree to which B cell responses within infected individuals can differ to two antigens from the same virus. Drawing on studies in other human and murine infections, including emerging data from COVID‐19, we consider the influence of antigen quantity and structure on the quality of the B cell response, the role of differential CD4 help, the importance of germinal center vs extrafollicular responses and the emerging concept that responses residing in non‐lymphoid organs can participate in B cell memory.
Highlights
Antigen-specific antiviral B cell responses are a key component in the resolution of viral infections and maintenance of immune memory following pathogen clearance or immunisation
Effective and durable humoral responses are generated in germinal center (GC) reactions, whereby B cells undergo iterative rounds of clonal expansion and somatic hypermutation to generate a diverse pool of memory B cells and plasma cells
While the GC has remained the focus of B cell research, it has long been appreciated that antibody responses can develop outside of the B cell follicle in the absence of notable GCs
Summary
Human antiviral B cell responses: Emerging lessons from hepatitis B and COVID-19. Division of Infection and Immunity, UCL, London, UK. Funding information Wellcome Trust, Grant/Award Number: 101849/Z/13/A; Efficacy and Mechanism Evaluation Programme
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