Lung-resident memory B cells established after pulmonary influenza infection display distinct transcriptional and phenotypic profiles.
Hyon-Xhi TanJennifer J JunoRobyn EsterbauerHannah G KellyKathleen M WraggPenny KonstandopoulosSheilajen AlcantaraCarolina AlvaradoRobert JonesGraham StarkeyBoa Zhong WangOsamu YoshinoThomas K S TiangM Lindsay GraysonHelen OpdamRohit D'CostaAngela Vagonull nullLaura K MackayClaire L GordonDavid MasopustJoanna R GroomStephen J KentAdam K WheatleyPublished in: Science immunology (2022)
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 retention of 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 lungs are 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.
Keyphrases
- lymph node
- working memory
- gene expression
- endothelial cells
- poor prognosis
- transcription factor
- regulatory t cells
- immune response
- quality improvement
- sars cov
- skeletal muscle
- metabolic syndrome
- signaling pathway
- oxidative stress
- induced apoptosis
- binding protein
- induced pluripotent stem cells
- machine learning
- data analysis
- long non coding rna
- heat shock protein
- sentinel lymph node
- cell migration
- disease virus