tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Jennifer A Juno[SUP] 1 [/SUP], Robyn Esterbauer[SUP] 1 [/SUP], Hannah G Kelly[SUP] 1 2 [/SUP], Kathleen M Wragg[SUP] 1 [/SUP], Penny Konstandopoulos[SUP] 1 [/SUP], Sheilajen Alcantara[SUP] 1 2 [/SUP], Carolina Alvarado[SUP] 3 [/SUP], Robert Jones[SUP] 4 [/SUP], Graham Starkey[SUP] 4 [/SUP], Boa Zhong Wang[SUP] 4 [/SUP], Osamu Yoshino[SUP] 4 [/SUP], Thomas Tiang[SUP] 4 [/SUP], M Lindsay Grayson[SUP] 5 [/SUP], Helen Opdam[SUP] 6 7 [/SUP], Rohit D'Costa[SUP] 8 9 [/SUP], Angela Vago[SUP] 4 [/SUP], Austin Liver Transplant Perfusionist Group; Laura K Mackay[SUP] 1 [/SUP], Claire L Gordon[SUP] 1 5 [/SUP], David Masopust[SUP] 10 11 [/SUP], Joanna R Groom[SUP] 3 12 [/SUP], Stephen J Kent[SUP] 1 2 13 [/SUP], Adam K Wheatley[SUP] 1 2 [/SUP]
Affiliations
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[SUB]RM[/SUB]) that are stably maintained in the lungs of mice after pulmonary influenza infection. Influenza-specific B[SUB]RM[/SUB] 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[SUB]RM[/SUB]. We found that CCR6 facilitates increased recruitment and/or retention of B[SUB]RM[/SUB] 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[SUB]RM[/SUB] 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[SUB]RM[/SUB] may constitute a discrete component of B cell immunity, positioned at the lung mucosa for rapid humoral response against respiratory viral infections.
. 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[SUP] 1 [/SUP], Jennifer A Juno[SUP] 1 [/SUP], Robyn Esterbauer[SUP] 1 [/SUP], Hannah G Kelly[SUP] 1 2 [/SUP], Kathleen M Wragg[SUP] 1 [/SUP], Penny Konstandopoulos[SUP] 1 [/SUP], Sheilajen Alcantara[SUP] 1 2 [/SUP], Carolina Alvarado[SUP] 3 [/SUP], Robert Jones[SUP] 4 [/SUP], Graham Starkey[SUP] 4 [/SUP], Boa Zhong Wang[SUP] 4 [/SUP], Osamu Yoshino[SUP] 4 [/SUP], Thomas Tiang[SUP] 4 [/SUP], M Lindsay Grayson[SUP] 5 [/SUP], Helen Opdam[SUP] 6 7 [/SUP], Rohit D'Costa[SUP] 8 9 [/SUP], Angela Vago[SUP] 4 [/SUP], Austin Liver Transplant Perfusionist Group; Laura K Mackay[SUP] 1 [/SUP], Claire L Gordon[SUP] 1 5 [/SUP], David Masopust[SUP] 10 11 [/SUP], Joanna R Groom[SUP] 3 12 [/SUP], Stephen J Kent[SUP] 1 2 13 [/SUP], Adam K Wheatley[SUP] 1 2 [/SUP]
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[SUB]RM[/SUB]) that are stably maintained in the lungs of mice after pulmonary influenza infection. Influenza-specific B[SUB]RM[/SUB] 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[SUB]RM[/SUB]. We found that CCR6 facilitates increased recruitment and/or retention of B[SUB]RM[/SUB] 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[SUB]RM[/SUB] 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[SUB]RM[/SUB] may constitute a discrete component of B cell immunity, positioned at the lung mucosa for rapid humoral response against respiratory viral infections.