Memory B cells in the lung participate in protective humoral immune responses to pulmonary influenza virus reinfection

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 109; no. 7; pp. 2485 - 2490
• Main Authors: Onodera, Taishi, Takahashi, Yoshimasa, Yokoi, Yusuke, Ato, Manabu, Kodama, Yuichi, Hachimura, Satoshi, Kurosaki, Tomohiro, Kobayashi, Kazuo
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 14.02.2012; National Acad Sciences
• Subjects: Antibody Formation; B lymphocytes; B-Lymphocytes - immunology; Biological Sciences; CD69 antigen; CD73 antigen; CD80 antigen; Correlation analysis; CXCR3 protein; Data processing; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Genotype & phenotype; hosts; Humans; immune response; Immune response (humoral); Immunoglobulin A; Immunoglobulin A - immunology; Immunoglobulin G; Immunoglobulin G - immunology; Immunologic Memory; Immunological memory; Infection; Infections; Influenza; Influenza A virus; Influenza virus; Influenza, Human - immunology; Lung; Lung - cytology; Lung - immunology; Lung diseases; Lung Diseases - immunology; Lungs; Lymphocytes B; Lymphocytes T; Memory cells; Mice; neutralization; neutralizing antibodies; Orthomyxoviridae; phenotype; Phenotypes; Plasma cells; Reinfection; Spleen; Surface markers; T cell receptors; T-lymphocytes; Viruses
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1115369109

After pulmonary virus infection, virus-binding B cells ectopically accumulate in the lung. However, their contribution to protective immunity against reinfecting viruses remains unknown. Here, we show the phenotypes and protective functions of virus-binding memory B cells that persist in the lung following pulmonary infection with influenza virus. A fraction of virus-binding B-cell population in the lung expressed surface markers for splenic mature memory B cells (CD73, CD80, and CD273) along with CD69 and CXCR3 that are up-regulated on lung effector/memory T cells. The lung B-cell population with memory phenotype persisted for more than 5 mo after infection, and on reinfection promptly differentiated into plasma cells that produced virus-neutralizing antibodies locally. This production of local IgG and IgA neutralizing antibody was correlated with reduced virus spread in adapted hosts. Our data demonstrates that infected lungs harbor a memory B-cell subset with distinctive phenotype and ability to provide protection against pulmonary virus reinfection.