Antibody levels poorly reflect on the frequency of memory B cells generated following SARS-CoV-2, seasonal influenza, or EBV infection

Abstract Assessment of humoral immunity is commonly confined to measurements of serum antibody reactivity. These pre-formed immunoglobulin molecules can convey immunity by preventing a re-infection. In some instances, however, a re-infection does occur, and in such cases, it is the mobilization of an anamnestic B and T cell response that confers immune protection. Relying on fundamentally different mechanisms, therefore, passive immunity conveyed by pre-existing antibodies needs to be distinguished from active B cell memory. Here, we tested whether in healthy human individuals the antibody titers to SARS-CoV-2, seasonal influenza, or Epstein-Barr virus antigens correlated with the frequency of memory B cells reactive with the respective antigens. Weak correlations were found. The data suggest that assessment of humoral immunity by measurement of antibody levels does not reflect on memory B cell frequencies, and thus an individual’s potential to engage into an anamnestic antibody response against the same or an antigenically-related virus. Direct monitoring of the antigen-reactive memory B cell compartment is both required and feasible towards that goal. Word Count = 166