Humoral immunity is an important constituent of the coordinated response essential to treat viral infections and mediate protection following pathogen clearance or vaccination. An improved elucidation of factors responsible for the memory B cell response have the potential to develop  effective preventative vaccines against emerging acute viral infections, therapeutic vaccines, and immunotherapies for chronic viral infections.

The authors of the present study included data extracted by profiling antigen-specific B cell responses in hepatitis B as a framework to evaluate lessons that can be understood from different viral infections about the various effects on humoral immunity. Hepatitis B, in addition, offers a paradigm where positive B cell responses in resolved or vaccinated individuals can be compared to the failed response in chronic infection. The investigators also contrasted and analysed the degree to which B cell responses within infected individuals can differ to two antigens from the same virus. The studies in correspond to other studies in other human and experimental infections, including emerging information from COVID-19, analyzed the impact of antigen quantity and structure on the quality of the B cell response, the role of differential CD4 help, the importance of the difference between germinal center and extrafollicular responses, and the emerging concept that responses residing in non-lymphoid organs can participate in B cell memory.

The study deduced that recognition of continuous HBsAg‐specific memory B cells has enhanced the likelihood that endogenous humoral immunity could be improved by analysing the defects and preventing their function in a chronic infection like CHB where anti‐HBs antibodies are undetectable. Currently available evidences that used fluorescent baits to characterize antigen‐specific B cell responses from patients with acute infections like COVID‐19 and chronic infections like HBV have magnified the understanding of the complexity of memory B cell responses. Flow cytometric analysis has permitted their ex vivo quantification and phenotypic characterization, revealing memory subsets with different isotype expression, homing patterns, and signatures of T_FH interactions and GC reactions, as well as transcriptional factors evaluating antiviral potential such as T‐bet.

On the contrary, the level of characterization of memory B cells is delayed behind T cells in viral infections and needs further studies. Besides targeted phenotypic analysis, unbiased profiling combining RNA‐sequencing with B cell receptor analysis permits more all-inclusive characterization of memory B cell responses. Determination of B cells specific for different viral antigens, carried out along with antigen‐specific T_FH responses and focused analysis of pathways such as CD40/CD40‐L, can aid in appraisal of their potential for productive interaction. Furthermore, parallel examination of memory B cell and plasma cell responses in lymph nodes, gut and bone marrow can provide a better knowledge of how well circulating frequencies and phenotypes reveal humoral antiviral immunity sequestered in these compartments.

Source: Burton AR, Maini MK. Human antiviral B cell responses: Emerging lessons from hepatitis B and COVID-19. Immunol Rev. 2021;299(1):108-117.