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Tetrameric and Homodimeric Camelid IgGs Originate from the Same IgH Locus

Ikbel Achour^*, Patricia Cavelier, Magali Tichit, Christiane Bouchier, Pierre Lafaye^* and François Rougeon^1,*

^* Unité de Génétique et Biochimie du Développement, Département d’Immunologie, Unité de Recherche Associée Centre National de la Recherche Scientifique 2581 and Plate-forme Génomique, Pasteur Génopole Ile-de-France, Institut Pasteur, Paris, France; and Service Transgenèse et Technologies Associées, Unité Mixte de Recherche C5535 Institut de Génétique Moléculaire de Montpellier, Montpellier, France

In addition to producing conventional tetrameric IgGs, camelids have the particularity of producing a functional homodimeric IgG type lacking L (light) chains and only made up of two H (heavy) chains. This nonconventional IgG type is characterized by variable and constant regions referred to as V_HH and C_HH, respectively, and which differ from conventional V_H and C_H counterparts. Although the structural properties of homodimeric IgGs have been well investigated, the genetic bases involved in their generation are still largely unknown. In this study, we characterized the organization of genes coding for the H chains of tetrameric and homodimeric IgGs by constructing an alpaca (Lama pacos) genomic cosmid library. We showed that a single IgH locus in alpaca chromosome 4 contains all of the genetic elements required for the generation of the two types of Igs. The alpaca IgH locus is composed of a V region that contains both V_HH and V_H genes followed by a unique D_H-J_H cluster and C region genes, which include both C_HH and C_H genes. Although this general gene organization greatly resembles that of other typical mammalian V_n-D_n-J_n-C_n translocon IgH loci, the intermixed gene organization within the alpaca V and C regions reveals a new type of translocon IgH locus. Furthermore, analyses of cDNA coding for the membrane forms of IgG and IgM present in alpaca peripheral blood B cells are most consistent with the notion that the development of a B cell bearing homodimeric IgG passes through an IgM⁺ stage, similar to the case for conventional IgG.

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.

¹ Address correspondence and reprint requests to Dr. François Rougeon, Unité de Génétique et Biochimie du Développement, Département d’Immunologie, Unité de Recherche Associée Centre National de la Recherche Scientifique 2581, Institut Pasteur, 25 rue du Dr. Roux 75724 Paris Cedex 15, France. E-mail address: frougeon{at}pasteur.fr

² Abbreviations used in this paper: FR, framework region; BLAST, basic local alignment search tool; IMGT, ImMunoGeneTics information system; FISH, fluorescence in situ hybridization; RSS, recombination signal sequence; sIg, surface Ig; S region, switch region.

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