Persistent IgG1 clones dominate and personalize the plasma antibody repertoire

Antibodies play a pivotal role in the immune defense and long-term immunity. Yet, while several studies have highlighted the persistence of antigen-specific antibody responses, it is unclear whether this stems from the continuous production of the same clones or recurrent activation of B cells generating new clones. To examine the stability of the human antibody repertoire, we monitored the concentrations of the most abundant IgG1 clones in plasma samples of 11 healthy donors at nine sampling points over a year. During this year, each donor received three doses of a COVID-19 vaccine. Notwithstanding these vaccinations, the concentrations of the most abundant IgG1 clones remained constant. Given the 2- to 3-week half-life of IgG1 molecules in blood, our data suggest that these clones are associated with long-term immunity and do not undergo somatic hypermutation which would imply short-lived plasma cells. Overall, our data suggest that most of the abundant IgG1 clones in plasma are persistently produced by long-lived plasma cells.