The IgH 3′ regulatory region controls somatic hypermutation in germinal center B cells
| Autor: | Alexis Saintamand, Yves Denizot, Michel Cogné, Christelle Vincent-Fabert, Bernardo Reina-San-Martin, Pauline Rouaud, Isabelle Robert, Rémi Fiancette, Eric Pinaud, Marie Marquet |
|---|---|
| Přispěvatelé: | Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2013 |
| Předmět: |
MESH: VDJ Exons
Transcription Genetic Immunoglobulin Variable Region MESH: Immunoglobulin Variable Region Gene Expression Regulatory Sequences Nucleic Acid MESH: Mice Knockout Mice 0302 clinical medicine MESH: Germinal Center Immunology and Allergy MESH: Animals 3' Untranslated Regions MESH: Chromatin Immunoprecipitation Mice Knockout B-Lymphocytes 0303 health sciences MESH: 3' Untranslated Regions Cytidine deaminase MESH: Gene Expression Regulation [SDV.IMM]Life Sciences [q-bio]/Immunology Immunoglobulin Heavy Chains MESH: Immunoglobulin Heavy Chains MESH: Somatic Hypermutation Immunoglobulin Chromatin Immunoprecipitation MESH: Gene Expression Immunology MESH: Immunoglobulin kappa-Chains Somatic hypermutation Biology Immunoglobulin light chain Immunoglobulin kappa-Chains 03 medical and health sciences MESH: B-Lymphocytes Cytidine Deaminase MESH: Regulatory Sequences Nucleic Acid Animals Enhancer MESH: Mice Central element MESH: Cytidine Deaminase 030304 developmental biology MESH: Transcription Genetic Brief Definitive Report Germinal center Germinal Center Molecular biology Gene Expression Regulation Immunoglobulin class switching Immunoglobulin heavy chain VDJ Exons Somatic Hypermutation Immunoglobulin 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine Journal of Experimental Medicine Journal of Experimental Medicine, Rockefeller University Press, 2013, 210 (8), pp.1501-7. ⟨10.1084/jem.20130072⟩ |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20130072 |
| Popis: | Somatic hypermutation in variable heavy chain rearranged regions is abrogated in the absence of the 3′ regulatory region enhancer, whereas transcription rate in the Ig heavy chain is only partially reduced. Interactions with cognate antigens recruit activated B cells into germinal centers where they undergo somatic hypermutation (SHM) in V(D)J exons for the generation of high-affinity antibodies. The contribution of IgH transcriptional enhancers in SHM is unclear. The Eμ enhancer upstream of Cμ has a marginal role, whereas the influence of the IgH 3′ regulatory region (3′RR) enhancers (hs3a, hs1,2, hs3b, and hs4) is controversial. To clarify the latter issue, we analyzed mice lacking the whole 30-kb extent of the IgH 3′RR. We show that SHM in VH rearranged regions is almost totally abrogated in 3′RR-deficient mice, whereas the simultaneous Ig heavy chain transcription rate is only partially reduced. In contrast, SHM in κ light chain genes remains unaltered, acquitting for any global SHM defect in our model. Beyond class switch recombination, the IgH 3′RR is a central element that controls heavy chain accessibility to activation-induced deaminase modifications including SHM. |
| Databáze: | OpenAIRE |
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