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

• Published in: Nature immunology Vol. 20; no. 1; pp. 97 - 108
• Main Authors: Allie, S. Rameeza, Bradley, John E., Mudunuru, Uma, Schultz, Michael D., Graf, Beth A., Lund, Frances E., Randall, Troy D.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-01-2019; Nature Publishing Group
• Subjects: 631/250/1619/40; 631/250/2152; 631/250/255; 631/250/347; Animals; Antigens; Antigens, Viral - immunology; B cells; B-Lymphocytes - immunology; Biomedical and Life Sciences; Biomedicine; Cell Differentiation; Cells, Cultured; Cellular signal transduction; Computer memory; Female; Gene expression; Humans; Immunity, Humoral; Immunologic Memory; Immunological memory; Immunology; Infection; Infections; Infectious Diseases; Influenza; Influenza vaccines; Influenza Vaccines - immunology; Influenza viruses; Influenza, Human - immunology; Lung; Lung - immunology; Lung - virology; Lung diseases; Lungs; Lymphocyte Activation; Lymphocytes B; Lymphoid tissue; Male; Memory cells; Mice; Mice, Inbred C57BL; Mice, Transgenic; Orthomyxoviridae - physiology; Orthomyxoviridae Infections - immunology; Plasma Cells - immunology; Secondary infection
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/s41590-018-0260-6

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.
Tissue-resident memory cells are functionally distinct from lymph node memory cells. Randall and colleagues show that lung infection establishes B cell memory in situ and confers superior responses following challenge infection, which will inform vaccine design for respiratory viruses.