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¹ Department of Pulmonary Medicine and ² Department of Virology, Erasmus University Medical Center, Rotterdam 3000 CA, Netherlands
³ Laboratory of Immunoregulation and Mucosal Immunology, Department of Respiratory Diseases, and ⁴ Laboratory of Molecular Immunology, University Ghent, Ghent B-9000, Belgium
⁵ Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, Netherlands

CORRESPONDENCE Bart N. Lambrecht: bart.lambrecht{at}ugent.be

Tertiary lymphoid organs (TLOs) are organized aggregates of B and T cells formed in postembryonic life in response to chronic immune responses to infectious agents or self-antigens. Although CD11c⁺ dendritic cells (DCs) are consistently found in regions of TLO, their contribution to TLO organization has not been studied in detail. We found that CD11c^hi DCs are essential for the maintenance of inducible bronchus-associated lymphoid tissue (iBALT), a form of TLO induced in the lungs after influenza virus infection. Elimination of DCs after the virus had been cleared from the lung resulted in iBALT disintegration and reduction in germinal center (GC) reactions, which led to significantly reduced numbers of class-switched plasma cells in the lung and bone marrow and reduction in protective antiviral serum immunoglobulins. Mechanistically, DCs isolated from the lungs of mice with iBALT no longer presented viral antigens to T cells but were a source of lymphotoxin (LT) β and homeostatic chemokines (CXCL-12 and -13 and CCL-19 and -21) known to contribute to TLO organization. Like depletion of DCs, blockade of LTβ receptor signaling after virus clearance led to disintegration of iBALT and GC reactions. Together, our data reveal a previously unappreciated function of lung DCs in iBALT homeostasis and humoral immunity to influenza virus.

Abbreviations used: BALf, bronchoalveolar lavage fluid; cDC, conventional DC; dpi, day post infection; DT, diphtheria toxin; DTR, DT receptor; FDC, follicular DC; GC, germinal center; HA, hemagglutinin; iBALT, inducible bronchus-associated lymphoid tissue; i.t., intratracheally; NP, nucleoprotein; SLO, secondary lymphoid organ; TLO, tertiary lymphoid organ.

© 2009 GeurtsvanKessel et al.
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