1. Tetrameric and homodimeric camelid IgGs originate from the same IgH locus
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Pierre Lafaye, Patricia Cavelier, Ikbel Achour, François Rougeon, Christiane Bouchier, Magali Tichit, Génétique et Biochimie du Développement, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Génomique (Plate-Forme), Institut Pasteur [Paris], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Génomique (Plate-Forme) - Genomics Platform, Institut Pasteur [Paris] (IP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
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MESH: Immunoglobulins ,MESH : Molecular Sequence Data ,MESH: Amino Acid Sequence ,MESH: Base Sequence ,MESH : Immunoglobulins ,0302 clinical medicine ,Immunology and Allergy ,MESH: Animals ,MESH: Phylogeny ,Peptide sequence ,Phylogeny ,Genetics ,0303 health sciences ,B-Lymphocytes ,biology ,MESH : Amino Acid Sequence ,MESH: Camels ,MESH : Protein Binding ,Translocon ,medicine.anatomical_structure ,MESH : Dimerization ,Cosmid ,MESH: Camelids, New World ,Antibody ,Camelids, New World ,Dimerization ,Protein Binding ,Camelus ,MESH : Cell Membrane ,Immunology ,Molecular Sequence Data ,Immunoglobulins ,[ SDV.IMM.IMM ] Life Sciences [q-bio]/Immunology/Immunotherapy ,MESH : B-Lymphocytes ,03 medical and health sciences ,Complementary DNA ,MESH: B-Lymphocytes ,medicine ,MESH: Protein Binding ,Animals ,Amino Acid Sequence ,Gene ,B cell ,030304 developmental biology ,MESH: Molecular Sequence Data ,MESH : Camels ,Base Sequence ,Cell Membrane ,MESH : Phylogeny ,[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy ,Molecular biology ,MESH : Camelids, New World ,Chromosome 4 ,MESH: Dimerization ,biology.protein ,MESH : Base Sequence ,MESH : Animals ,030215 immunology ,MESH: Cell Membrane - Abstract
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 VHH and CHH, respectively, and which differ from conventional VH and CH 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 VHH and VH genes followed by a unique DH-JH cluster and C region genes, which include both CHH and CH genes. Although this general gene organization greatly resembles that of other typical mammalian Vn-Dn-Jn-Cn 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.
- Published
- 2008
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