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

Hyon Xhi Tan, Jennifer A. Juno, Robyn Esterbauer, Hannah G. Kelly, Kathleen M. Wragg, Penny Konstandopoulos, Sheilajen Alcantara, Carolina Alvarado, Robert Jones, Graham Starkey, Boa Zhong Wang, Osamu Yoshino, Thomas Tiang, M. Lindsay Grayson, Helen Opdam, Rohit D'Costa, Angela Vago, Laura K. Mackay, Claire L. Gordon, David MasopustJoanna R. Groom, Stephen J. Kent, Adam K. Wheatley

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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 (BRM) that are stably maintained in the lungs of mice after pulmonary influenza infection. Influenza-specific BRM 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 BRM. We found that CCR6 facilitates increased recruitment and/or retention of BRM 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 BRM 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 BRM may constitute a discrete component of B cell immunity, positioned at the lung mucosa for rapid humoral response against respiratory viral infections.

Original languageEnglish (US)
Article numbereabf5314
JournalScience Immunology
Volume7
Issue number67
DOIs
StatePublished - Jan 2022

Bibliographical note

Publisher Copyright:
© 2022 American Association for the Advancement of Science. All rights reserved.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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