Quantitative and Qualitative Analysis of Humoral Immunity Reveals Continued and Personalized Evolution in Chronic Viral Infection
During established chronic viral infections, tailored virus-specific antibody responses can promote its eventual control. The extent to which the ensemble of antibodies has to evolve to this end during chronic infection is unclear. A collaborative "Cell Reports" paper by the Oxenius (IMB), Reddy and Stadler (D-BSSE) groups sheds light on the dynamics of antibody responses during acute and chronic viral infections.
Control of established chronic infection with lymphocytic choriomeningitis virus (LCMV) requires the production of neutralizing antibodies (abs), but is not known how the ensemble of abs evolves during ongoing infection to finally generate abs with neutralizing quality. Using a combination of quantitative functional assays and time-resolved ab repertoire sequencing allowed the longitudinal tracking of ab responses in individual hosts with acute or chronic LCMV infection. This revealed that ab repertoires were initially very similar in acute and chronic LCMV infection, however, with time, the repertoires diverged in a personalized manner between individual chronically infected hosts. This personalized response was accompanied with sustained activity of structure-function units (germinal centers) which promote continued inclusion and selection of ab-producing cells, eventually leading to the emergence of ab-producing cells with increased output of abs exhibiting increased affinity for viral antigens. These data support the concept that fostering ab-producing cell diversity throughout chronic infection correlates with the development of infection-resolving abs.
Link to the publication in "external page Cell Reports"
Graphical abstract
Acute and chronic LCMV infection induce massive clonal expansion of multiple ab-producing clones (B cells) that converge in their composition during early stages of infection (red / orange / pink B cells). During later stages of infection, the initially induced B cell repertoires vanishes from the circulation in acutely infected mice (yellow background), while it is preserved long-term in individuals being chronically infected (blue background). However, these repertoires continuously evolve to adapt a personalized repertoire (indicated by green, purple and blue color in individual mice) in chronically infected mice, selecting cells with higher secretion rates of high affinity LCMV-specific antibodies.