Lung-resident memory B cells established after pulmonary influenza infection display distinct transcriptional and phenotypic profiles

摘要

Recent studies have established that memory B cells, largely thought to be circulatory in the blood, can take up long-term residency in inflamed tissues, analogous to widely described tissue-resident T cells. The dynamics of recruitment and retentionof memory B cells to tissues and their immunological purpose remains unclear. Here, we characterized tissue-resident memory B cells (B_(RM)) that are stably maintained in the lungs of mice after pulmonary influenza infection. Influenza-specific B_(RM) were localized within inducible bronchus-associated lymphoid tissues (iBALTs) and displayed transcriptional signatures distinct from classical memory B cells in the blood or spleen while showing partial overlap with memory B cells in lung-draining lymph nodes. We identified lung-resident markers, including elevated expression of CXCR3, CCR6, and CD69, on hemagglutinin (HA)– and nucleoprotein (NP)–specific lung B_(RM). We found that CCR6 facilitates increased recruitment and/or retention of B_(RM) in lungs and differentiation into antibody-secreting cells upon recall. Although expression of CXCR3 and CCR6 was comparable in total and influenza-specific memory B cells isolated across tissues of human donors, CD69 expression was higher in memory B cells from lung and draining lymph nodes of human organ donors relative to splenic and PBMC-derived populations, indicating that mechanisms underpinning B_(RM) localization may be evolutionarily conserved. Last, we demonstrate that human memory B cells in lungsare transcriptionally distinct to populations in lung-draining lymph nodes or PBMCs. These data suggest that B_(RM) may constitute a discrete component of B cell immunity, positioned at the lung mucosa for rapid humoral response against respiratory viral infections.