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 Alcântara, Carolina Alvarado, Robert M. Jones, Graham Starkey, Boa Zhong Wang, Osamu Yoshino, Thomas Tiang, M. Lindsay Grayson, Helen Opdam, Rohit D’Costa, Angela Vago, the Austin Liver Transplant Perfusionist Group, Laura K. Mackay, Claire L. Gordon, David Masopust, Joanna R. Groom, Stephen J. Kent, Adam K. Wheatley
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.