title: The Eμ enhancer region influences H chain expression and B cell fate without impacting IgVH repertoire and immune response in vivo.
abstract: The IgH intronic enhancer region Eμ is a combination of both a 220-bp core enhancer element and two 310-350-bp flanking scaffold/matrix attachment regions named MARsEμ. In the mouse, deletion of the core-enhancer Eμ element mainly affects VDJ recombination with minor effects on class switch recombination. We carried out endogenous deletion of the full-length Eμ region (core plus MARsEμ) in the mouse genome to study VH gene repertoire and IgH expression in developing B-lineage cells. Despite a severe defect in VDJ recombination with partial blockade at the pro-B cell stage, Eμ deletion (core or full length) did not affect VH gene usage. Deletion of this regulatory region induced both a decrease of pre-B cell and newly formed B cell compartments and a strong orientation toward the marginal zone B cell subset. Because Igμ H chain expression was decreased in Eμ-deficient pre-B cells, we propose that modification of B cell homeostasis in deficient animals was caused by "weak" pre-B cell and BCR expression. Besides imbalances in B cell compartments, Ag-specific Ab responses were not impaired in animals carrying the Eμ deletion. In addition to its role in VDJ recombination, our study points out that the full-length Eμ region does not influence VH segment usage but ensures efficient Igμ-chain expression required for strong signaling through pre-B cells and newly formed BCRs and thus participates in B cell inflow and fate.
authors: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7276, Université de Limoges, 87025 Limoges, France;
authors: Marie
authors: M
authors: Marquet
authors: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7276, Université de Limoges, 87025 Limoges, France;
authors: Armand
authors: A
authors: Garot
authors: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7276, Université de Limoges, 87025 Limoges, France; Centre Hospitalier Universitaire Dupuytren, Centre de Référence des Amyloses, 87042 Limoges, France; and.
authors: Sébastien
authors: S
authors: Bender
authors: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7276, Université de Limoges, 87025 Limoges, France;
authors: Claire
authors: C
authors: Carrion
authors: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7276, Université de Limoges, 87025 Limoges, France;
authors: Pauline
authors: P
authors: Rouaud
authors: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7276, Université de Limoges, 87025 Limoges, France;
authors: Sandrine
authors: S
authors: Lecardeur
authors: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7276, Université de Limoges, 87025 Limoges, France;
authors: Yves
authors: Y
authors: Denizot
authors: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7276, Université de Limoges, 87025 Limoges, France; Institut Universitaire de France, 75005 Paris, France.
authors: Michel
authors: M
authors: Cogné
authors: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7276, Université de Limoges, 87025 Limoges, France; eric.pinaud@unilim.fr.
authors: Eric
authors: E
authors: Pinaud
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D004742:Enhancer Elements, Genetic / Q000276:immunology*; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000276:immunology*; D050438:Genes, Immunoglobulin Heavy Chain / Q000276:immunology*; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D011897:Random Allocation; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D060152:V(D)J Recombination / Q000235:genetics / Q000276:immunology
chemical_list: D007135:Immunoglobulin Variable Region; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell