GSE174682
Bona fide and bystander memory B cell subsets colonize the lung peribronchial niche upon viral infection
Memory B cells (MBCs) are key cellular components of long-term humoral immunity that dominate recall responses by rapidly differentiating into effector cells. As the biology of MBCs has been mainly studied in the context of model antigen immunizations, the dynamics of these cells during infection remains largely unexplored. Here, we combined influenza and SARS-CoV-2 infection models with fluorescent-reporter mice to identify MBCs regardless of antigen-specificity. scRNA-seq analysis and confocal imaging revealed that two main transcriptionally distinct subsets of MBCs colonize the lung airways after infection. These subsets were class-switched, somatically mutated and preferentially differentiated into plasma rather than germinal center cells upon activation. Combined analysis of antigen-specificity and B cell receptor repertoire unveiled a highly permissive selection process that segregated these subsets into “bona fide” virus-specific MBCs and “bystander” MBCs with no apparent specificity for eliciting viruses. Thus, diverse transcriptional programs in MBCs are not linked to specific effector fates but rather to divergent strategies of the immune system to simultaneously provide rapid protection from re-infection while diversifying the initial B cell repertoire. Overall design: Memory B cells were FACS-sorted from lungs, mediastinal lymph nodes, or spleen of Aicda-Cre-ERT2 x Rosa26-LSL-eYFP mice 70 days after intranasal infection with influenza A virus PR8 H1N1 strain, and subjected to single-cell RNA-seq by either droplet-based 10x Genomics 5'-end protocol, or plate-based FB5P-seq 5'-end protocol.