The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1996/12/2353/ $5.00
The Journal of Experimental Medicine, Volume 184, Number 6, December 1, 1996 2353-2360

Articles

Germinal Center Formation and Local Immunoglobulin E (IgE) Production in the Lung after an Airway Antigenic Challenge

Yolande Chvatchko*, Marie H. Kosco-Vilbois*, Suzanne Herren*, Jean Lefort{ddagger}, and Jean-Yves Bonnefoy*

From the * Department of Immunology, Geneva Biomedical Research Institute, Glaxo Wellcome Research and Development S.A., Ch-1228 Plan-les-Ouates, Geneva, Switzerland, and the {ddagger} Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur, Institut National de la Santé et de la Recherche Médicale, U 285, 75724 Paris, France

Airway inflammation plays a central role in the pathogenesis of asthma. However, the precise contribution of all cell types in the development and maintenance of airway hyperreactivity and histopathology during allergic inflammation remains unclear. After sensitization of mice in the periphery, challenge by multiple intratracheal (i.t.) instillations of ovalbumin (OVA) results in eosinophilia, mononuclear cell infiltration, and airway epithelial changes analogous to that seen in asthma (Blyth, D.I., M.S. Pedrick, T.J. Savage, E.M. Hessel, and D. Fattah. 1996. Am. J. Respir. Cell Mol. Biol. 14:425–438). To investigate further the nature of the cellular infiltrate, lungs from OVA-versus saline-treated mice were processed for histology and immunohistochemistry. One of the most striking features observed was the formation of germinal centers within the parenchyma of the inflamed lungs. In addition, follicular dendritic cells (FDCs) bearing OVA on their plasma membranes appeared and, adjacent to these sites, OVA-specific IgG1-, IgE-, and IgA-producing plasma cells emerged. To confirm that antigen-specific immunoglobulins (Ig) were being produced within the parenchyma, plasma cell number and antibody production were quantitated in vitro after isolation of cells from the lung. These assays confirmed that the isotypes observed in situ were a secreted product. As IgE-dependent mechanisms have been implicated as being central to the pathogenesis of bronchial asthma, airway hyperresponsiveness was evaluated. The mice undergoing lung inflammation were hyperresponsive, while the control group remained at baseline. These data demonstrate that antigen-driven differentiation of B cells via induction of an FDC network and germinal centers occurs in the parenchyma of inflamed lungs. These germinal centers would then provide a local source of IgEsecreting plasma cells that contribute to the release of factors mediating inflammatory processes in the lung.

Address correspondence to Dr. M. Kosco-Vilbois, Immunology Department, Geneva Biomedical Research Institute, Glaxo Wellcome Research and Development S.A., 14 chemin des Aulx, Ch-1228 Plan-lesOuates, Geneva, Switzerland.

The authors wish to thank A.J. Coyle and C. Plater-Zyberk for helpful discussions in the preparation of this manuscript, D. Blyth for help in establishing the experimental murine model, and J. Knowles for continued support.

1Abbreviations used in this paper: PNA, peanut agglutinin; FDC, follicular dendritic cell; GALT, gut-associated lymphoid tissue; BALT, bronchusassociated lymphoid tissue; i.t., intratracheal; Penh, enhanced pause.

Y. Chvatchko and M. Kosco-Vilbois contributed equally to this work.


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