Memory B cell dynamics after respiratory viral infections

Abstract

Viral respiratory infections continue to be a global health burden with high mor- bidity and mortality. With two viral pandemics with only 10 years apart, by Influenza A virus, 2009, and SARS-CoV2 emerging 2019, and rapidly evolving viral pathogens, the next pandemic is not a question of if, but of when. As B cells provide critical protection against viral infections, this thesis aimed at stud- ying how B cells respond to viral respiratory infections and how they develop over time. Through a combination of flow cytometry and single cell sequencing and analysis of secreted and expressed antibodies, we created a detailed map of B cell development. We also studied whether secondary Streptococcus pneu- moniae infection influence the primary viral responses. In paper I, we found that memory B cells in the lung can originate from other lymphoid tissue and that high affinity B cells may generate both memory B cells and Plasma cells. In paper II, we discovered how a secondary infection disrupts the accumulation of memory B cells in the lungs and how that leads to a detri- mental outcome upon re-challenge. In paper III, we found a strong Plasmablast response after SARS-CoV2 infection that, based on their antigen specific and rapid onset points to differentiated memory B cell origin from endemic corona- viruses. This was further corroborated in paper IV, where, through clonal anal- ysis we could show rapid onset of highly mutated plasmablasts. Furthermore, we could show continued maturation of the B cell response over time. Taken together, this thesis contributes to better understanding of B cell development, and factors that influence B cell responses.