Viral infection engenders bona fide and bystander subsets of lung-resident memory B cells through a permissive mechanism

Lung-resident memory B cells (MBCs) provide localized protection against reinfection in respiratory airways. Currently, the biology of these cells remains largely unexplored. Here, we combined influenza and SARS-CoV-2 infection with fluorescent-reporter mice to identify MBCs regardless of antigen specificity. We found that two main transcriptionally distinct subsets of MBCs colonized the lung peribronchial niche after infec-tion. These subsets arose from different progenitors and were both class switched, somatically mutated, and intrinsically biased in their differentiation fate toward plasma cells. Combined analysis of antigen spec-ificity and B cell receptor repertoire segregated these subsets into ???bona fide???virus-specific MBCs and ???bystander???MBCs with no apparent specificity for eliciting viruses generated through an alternative permis-sive process. 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 reinfec-tion while diversifying the initial B cell repertoire.

Automated summary

This study investigated lung-resident memory B cells and identified two distinct transcriptional subsets with class switching, somatic mutation, and biased differentiation fate. The analysis of antigen specificity and B cell receptor repertoire revealed virus-specific and bystander subsets. The findings suggest that the transcriptional programs in MBCs are related to the immune system's strategies for providing protection and diversifying the B cell repertoire.