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J. Biol. Chem., Vol. 279, Issue 11, 10228-10236, March 12, 2004

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Binding of Free Immunoglobulin Light Chains to VpreB3 Inhibits Their Maturation and Secretion in Chicken B Cells^*

Olivier Rosnet, Carla Blanco-Betancourt, Karine Grivel, Kirsten Richter¶, and Claudine Schiff

From the Centre d'Immunologie de Marseille-Luminy, Centre National de la Recherche Scientifique-Institut National de la Santé et de la Recherche Médicale-Université de la Méditerranée, Campus de Luminy, 13288 Marseille Cedex 09, France

The VpreB3 gene product was first characterized as an immunoglobulin (Ig) µ heavy chain-binding protein in mouse precursor B (pre-B) cells. Although its function is unknown, it has been proposed to participate in the assembly and transport of the pre-B cell receptor. We have identified a VpreB3 orthologous gene in chicken that is located close to the immunoglobulin light chain (LC) gene cluster and specifically expressed in the bursa of Fabricius. By overexpressing VpreB3 in the DT40 IgM⁺ immature chicken B cell line, we have characterized VpreB3 as an endoplasmic reticulum-resident glycoprotein that binds preferentially to free IgLC. However, binding to IgHC is observed in IgLC-deficient DT40 cells. Interaction of VpreB3 with free IgLC is partly covalent and induces retention of free IgLC in the endoplasmic reticulum, preventing their secretion without affecting IgM surface expression. Our results demonstrate that this evolutionarily conserved molecule may play a role in the regulation of the maturation and secretion of free IgLC in B cells. We discuss possible implications in the regulation of the immune response.

Received for publication, November 6, 2003 , and in revised form, December 5, 2003.

^* This work was supported by INSERM, CNRS, and a grant from the Association pour la Recherche contre le Cancer (ARC). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Recipient of a fellowship from ARC and previously from Ministère de l'Enseignement Superieur et de la Recherche.

^¶ Present address: Dept. of Virology, University of Freiburg, D-79104 Freiburg, Germany.

To whom correspondence may be addressed: Centre d'Immunologie de Marseille-Luminy, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. Tel.: 33-4-9126-9448; Fax: 33-4-9126-9430; E-mail: rosnet{at}ciml.univ-mrs.fr or schiff{at}ciml.univ-mrs.fr.

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