Quantitative and Qualitative Analysis of Humoral Immunity Reveals Continued and Personalized Evolution in Chronic Viral Infection

Abstract

Summary: Control of established chronic lymphocytic choriomeningitis virus (LCMV) infection requires the production of neutralizing antibodies, but it remains unknown how the ensemble of antibodies evolves during ongoing infection. Here, we analyze the evolution of antibody responses during acute or chronic LCMV infection, combining quantitative functional assays and time-resolved antibody repertoire sequencing. We establish that antibody responses initially converge in both infection types on a functional and repertoire level, but diverge later during chronic infection, showing increased clonal diversity, the appearance of mouse-specific persistent clones, and distinct phylogenetic signatures. Chronic infection is characterized by a longer-lasting germinal center reaction and a continuous differentiation of plasma cells, resulting in the emergence of higher-affinity plasma cells exhibiting increased antibody secretion rates. Taken together, our findings reveal the emergence of a personalized antibody response in chronic infection and support the concept that maintaining B cell diversity throughout chronic LCMV infection correlates with the development of infection-resolving antibodies. : Kräutler et al. compare the evolutions of antibody responses during acute or chronic lymphocytic choriomeningitis (LCMV) infection by combining quantitative functional assays and time-resolved antibody repertoire sequencing. They reveal sustained germinal center (GC) reactions and plasma cell differentiation during chronic infection, leading to the emergence of a personalized antibody repertoire containing infection-resolving antibodies. Keywords: chronic viral infection, antibody repertoire, clonal diversity, sustained germinal center reaction, high affinity antibodies