Giuseppe
Emeritus
[Source: Proc Natl Acad Sci USA, full text: (LINK). Abstract, edited.]
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Memory B cells in the lung participate in protective humoral immune responses to pulmonary influenza virus reinfection
Taishi Onodera<SUP>a</SUP>, Yoshimasa Takahashi<SUP>a</SUP><SUP>1</SUP>, Yusuke Yokoi<SUP>a</SUP><SUP>b</SUP>, Manabu Ato<SUP>a</SUP>, Yuichi Kodama<SUP>a</SUP>, Satoshi Hachimura<SUP>b</SUP>, Tomohiro Kurosaki<SUP>c</SUP><SUP>d</SUP>, and Kazuo Kobayashi<SUP>a</SUP>
<SUP></SUP>
Author Affiliations: <SUP>a</SUP>Department of Immunology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan; <SUP>b</SUP>Research Center for Food Safety, Graduate School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan; <SUP>c</SUP>Laboratory of Lymphocyte Differentiation, World Premier International Immunology Frontier Research Center, and Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan; and <SUP>d</SUP>Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
Edited* by Michel C. Nussenzweig, The Rockefeller University, New York, NY, and approved December 29, 2011 (received for review September 18, 2011)
Abstract
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.
lung memory B cells - viral immunity
Footnotes
<SUP>1</SUP>To whom correspondence should be addressed. E-mail: ytakahas@nih.go.jp.
Author contributions: Y.T., M.A., S.H., T.K., and K.K. designed research; T.O., Y.T., Y.Y., and Y.K. performed research; T.O. and Y.T. analyzed data; and Y.T., T.K., and K.K. wrote the paper.
The authors declare no conflict of interest.
*This Direct Submission article had a prearranged editor.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1115369109/-/DCSupplemental.
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Author Affiliations: <SUP>a</SUP>Department of Immunology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan; <SUP>b</SUP>Research Center for Food Safety, Graduate School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan; <SUP>c</SUP>Laboratory of Lymphocyte Differentiation, World Premier International Immunology Frontier Research Center, and Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan; and <SUP>d</SUP>Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
Edited* by Michel C. Nussenzweig, The Rockefeller University, New York, NY, and approved December 29, 2011 (received for review September 18, 2011)
Abstract
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.
lung memory B cells - viral immunity
Footnotes
<SUP>1</SUP>To whom correspondence should be addressed. E-mail: ytakahas@nih.go.jp.
Author contributions: Y.T., M.A., S.H., T.K., and K.K. designed research; T.O., Y.T., Y.Y., and Y.K. performed research; T.O. and Y.T. analyzed data; and Y.T., T.K., and K.K. wrote the paper.
The authors declare no conflict of interest.
*This Direct Submission article had a prearranged editor.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1115369109/-/DCSupplemental.
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