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The establishment of resident memory B cells in the lung requires local antigen encounter.

ABSTRACT: Memory B cells are found in lymphoid and non-lymphoid tissues, suggesting that some may be tissue-resident cells. Here we show that pulmonary influenza infection elicited lung-resident memory B cells (BRM cells) that were phenotypically and functionally distinct from their systemic counterparts. BRM cells were established in the lung early after infection, in part because their placement required local antigen encounter. Lung BRM cells, but not systemic memory B cells, contributed to early plasmablast responses following challenge infection. Following secondary infection, antigen-specific BRM cells differentiated in situ, whereas antigen-non-specific BRM cells were maintained as memory cells. These data demonstrate that BRM cells are an important component of immunity to respiratory viruses such as influenza virus and suggest that vaccines designed to elicit BRM cells must deliver antigen to the lungs.

SUBMITTER: Allie SR

PROVIDER: S-EPMC6392030 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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The establishment of resident memory B cells in the lung requires local antigen encounter.

Allie S Rameeza SR Bradley John E JE Mudunuru Uma U Schultz Michael D MD Graf Beth A BA Lund Frances E FE Randall Troy D TD

Nature immunology 20181203 1

Memory B cells are found in lymphoid and non-lymphoid tissues, suggesting that some may be tissue-resident cells. Here we show that pulmonary influenza infection elicited lung-resident memory B cells (BRM cells) that were phenotypically and functionally distinct from their systemic counterparts. BRM cells were established in the lung early after infection, in part because their placement required local antigen encounter. Lung BRM cells, but not systemic memory B cells, contributed to early plasm ...[more]

PMID: 30510223

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Project description:While the brain is considered an immune-privileged site, the CNS may nevertheless be the focus of immune mediated inflammation in the case of infection and certain autoimmune diseases, e.g., multiple sclerosis. As in other tissues, it has been found that acute T-cell infiltration may be followed by establishment of persistent local T-cell memory. To improve our understanding regarding the regulation of putative tissue resident memory T (Trm) cells in CNS, we devised a new model system for studying the generation of Trm cells in this site. To this purpose, we exploited the fact that the CNS may be a sanctuary for adenoviral infection, and to minimize virus-induced disease, we chose replication-deficient adenoviruses for infection of the CNS. Non-replicating adenoviruses are known to be highly immunogenic, and our studies demonstrate that intracerebral inoculation causes marked local T-cell recruitment, which is followed by persistent infiltration of the CNS parenchyma by antigen specific CD8+ T cells. Phenotypical analysis of CNS infiltrating antigen specific CD8+ T cells was consistent with these cells being Trms. Regarding the long-term stability of the infiltrate, resident CD8+ T cells expressed high levels of the anti-apoptotic molecule Bcl-2 as well as the proliferation marker Ki-67 suggesting that the population is maintained through steady homeostatic proliferation. Functionally, memory CD8+ T cells from CNS matched peripheral memory cells with regard to capacity for ex vivo cytotoxicity and cytokine production. Most importantly, our experiments revealed a key role for local antigen encounter in the establishment of sustained CD8+ T-cell memory in the brain. Inflammation in the absence of cognate antigen only led to limited and transient infiltration by antigen specific CD8+ T cells. Together these results indicate that memory CD8+ T cells residing in the CNS predominantly mirror previous local infections and immune responses to local autoantigens.

Dataset Information

The establishment of resident memory B cells in the lung requires local antigen encounter.

Publications

The establishment of resident memory B cells in the lung requires local antigen encounter.

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