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Molecular and Cellular Biology, January 2005, p. 88-99, Vol. 25, No. 1
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.1.88-99.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Disruption of the langerin/CD207 Gene Abolishes Birbeck Granules without a Marked Loss of Langerhans Cell Function

Adrien Kissenpfennig,1 Smina Aït-Yahia,2 Valérie Clair-Moninot,2 Hella Stössel,3 Edgar Badell,4 Yann Bordat,4 Joanne L. Pooley,5 Thierry Lang,6 Eric Prina,6 Isabelle Coste,2 Olivia Gresser,1 Toufic Renno,2 Nathalie Winter,4 Geneviève Milon,6 Ken Shortman,5 Nikolaus Romani,3 Serge Lebecque,2 Bernard Malissen,1* Sem Saeland,2* and Patrice Douillard2

Centre d'Immunologie de Marseille-Luminy, INSERM-CNRS-Université de la Méditerranée, Parc Scientifique de Luminy, Marseille,1 Laboratory for Immunological Research, Schering Plough, Dardilly,2 Unité d'Immunophysiologie et Parasitisme Intracellulaire,6 Unité de Génétique Mycobactérienne, Institut Pasteur, Paris, France,4 Department of Dermatology, Innsbruck Medical University, Innsbruck, Austria,3 The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia5

Received 2 August 2004/ Returned for modification 3 September 2004/ Accepted 10 October 2004

Langerin is a C-type lectin expressed by a subset of dendritic leukocytes, the Langerhans cells (LC). Langerin is a cell surface receptor that induces the formation of an LC-specific organelle, the Birbeck granule (BG). We generated a langerin–/– mouse on a C57BL/6 background which did not display any macroscopic aberrant development. In the absence of langerin, LC were detected in normal numbers in the epidermis but the cells lacked BG. LC of langerin–/– mice did not present other phenotypic alterations compared to wild-type littermates. Functionally, the langerin–/– LC were able to capture antigen, to migrate towards skin draining lymph nodes, and to undergo phenotypic maturation. In addition, langerin–/– mice were not impaired in their capacity to process native OVA protein for I-Ab-restricted presentation to CD4+ T lymphocytes or for H-2Kb-restricted cross-presentation to CD8+ T lymphocytes. langerin–/– mice inoculated with mannosylated or skin-tropic microorganisms did not display an altered pathogen susceptibility. Finally, chemical mutagenesis resulted in a similar rate of skin tumor development in langerin–/– and wild-type mice. Overall, our data indicate that langerin and BG are dispensable for a number of LC functions. The langerin–/– C57BL/6 mouse should be a valuable model for further functional exploration of langerin and the role of BG.

* Corresponding author. Mailing address for Sem Saeland: Schering Plough, Laboratory for Immunological Research, 27, Chemin des Peupliers, BP 11, 69571 Dardilly cedex, France. Phone: 33 4 72 17 27 00. Fax: 33 4 78 35 47 50. E-mail: semsaeland{at}yahoo.fr. Mailing address for Bernard Malissen: Centre d'Immunologie de Marseille-Luminy, INSERM-CNRS-Université de la Méditerranée, Parc Scientifique de Luminy, 13288 Marseille Cedex 9, France. Phone: 33 491 26 94 78. Fax: 33 491 26 94 30. E-mail: bernardm{at}ciml.univ-mrs.fr.

Molecular and Cellular Biology, January 2005, p. 88-99, Vol. 25, No. 1
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.1.88-99.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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