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

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Sci Immunol


. 2022 Jan 28;7(67):eabf5314.
doi: 10.1126/sciimmunol.abf5314. Epub 2022 Jan 28.
Lung-resident memory B cells established after pulmonary influenza infection display distinct transcriptional and phenotypic profiles


Hyon-Xhi Tan ¹ , Jennifer A Juno ¹ , Robyn Esterbauer ¹ , Hannah G Kelly ^{1 2} , Kathleen M Wragg ¹ , Penny Konstandopoulos ¹ , Sheilajen Alcantara ^{1 2} , Carolina Alvarado ³ , Robert Jones ⁴ , Graham Starkey ⁴ , Boa Zhong Wang ⁴ , Osamu Yoshino ⁴ , Thomas Tiang ⁴ , M Lindsay Grayson ⁵ , Helen Opdam ^{6 7} , Rohit D'Costa ^{8 9} , Angela Vago ⁴ , Austin Liver Transplant Perfusionist Group; Laura K Mackay ¹ , Claire L Gordon ^{1 5} , David Masopust ^{10 11} , Joanna R Groom ^{3 12} , Stephen J Kent ^{1 2 13} , Adam K Wheatley ^{1 2}



Affiliations

• PMID: 35089815
• DOI: 10.1126/sciimmunol.abf5314

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 (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.