Human antiviral B cell responses: Emerging lessons from hepatitis B and COVID‐19

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.

The memory B cell response to influenza vaccination is impaired in older persons

“…The routes to FcRL5 expression and acquisition of an atypical memory phenotype are incompletely understood and likely context specific ( Burton and Maini, 2021 ). Our analysis of the data reported in Turner et al.…”

The Memory B Cell Response to Influenza Vaccination is Impaired in Older Persons

“…The routes to FcRL5 expression and acquisition of an atypical memory phenotype are incompletely understood and likely context specific (Burton and Maini, 2021). Our analysis of the data reported in Turner et al (2020) found relatively low levels of FCRL5 transcript expression by GC B cells, suggesting that FCRL5 expression may be gained either by positively selected cells on their egress from the GC or by antigen-specific B cells after B:T cell interaction on the edge of the follicle.…”

Double Negative (DN) B cells: A connecting bridge between rheumatic diseases and COVID-19?

“…However, a few studies have turned their attention to humoral immune responses, and thus investigated the role and function of B cells in the infection. 6 – 9 As in many other infectious diseases such as HIV, hepatitis B and malaria, 9 , 10 , 11 alterations of the B cell compartment have also been reported in COVID-19. 6 – 9 , 12 Interestingly, analyses of B cell populations revealed that extrafollicular double negative (DN) B cells, a characteristic of active systemic lupus erythematosus (SLE), 13 are a prominent feature of severe COVID-19 as well.…”

“… 6 – 9 As in many other infectious diseases such as HIV, hepatitis B and malaria, 9 , 10 , 11 alterations of the B cell compartment have also been reported in COVID-19. 6 – 9 , 12 Interestingly, analyses of B cell populations revealed that extrafollicular double negative (DN) B cells, a characteristic of active systemic lupus erythematosus (SLE), 13 are a prominent feature of severe COVID-19 as well. 7 , 12 , 14 , 15 Moreover, the frequencies of these DN cells correlate with disease severity profiles and some clinical and laboratory parameters of the disease.…”