Sophie Péron



Permanent researcher INSERM
Team 2MB2C

We are studying the link between genetic rearrangements of immunoglobulin genes and DNA repair in chronic lymphocytic leukemia.

Office 137 CBRS
05 19 56 42 10


Research activity

Chronic lymphoid leukemia (CLL) is a malignant blood disease caused by the monoclonal proliferation of mature B lymphocytes. According to the report “Les cancers en France” (Les cancers en France, Les Data / Epidémiologie. INCa, 2017), in 2012 in France there were 35,000 new cases of malignant hemopathies per year, half of which are lymphoid hemopathies. cancers of the B lymphocyte lineage. CLL is common in adults and results in lymphocytosis (increased lymphocyte count), circulatory and lymph node, which results in deregulation of the immune response, increasing the risk of infections and cancers . The oncogenic processes of CLL are not clearly defined.
Using a tool developed by our team (Boyer et al. , J Immunol. 2017) allowing the analysis of genetic recombinations of the heavy chain locus of immunoglobulins from high throughput sequencing data, chromatin immunoprecipitation techniques and by developing functional assays, we are analyzing DNA repair in tumor cells from patients with CLL.

Our goal is to understand the biological consequences of deregulation of DNA repair mechanisms in tumor transformation in CLL.

LB are “privileged” targets of DNA damage. During their development and when they are mature, LB undergo physiological mechanisms implicating DNA breaks and/or mutations of Ig genes. The V(D)J rearrangements that allow Ig expression, Ig class switch recombination (CSR), and IgH locus suicide recombination (LSR) are genetic recombinations of Ig chain loci. DNA damage response ensures genomic stability and inaccurate DNA repair underlies various diseases, ranging from developmental disorders to cancer. Our project uses B-cell physiological processes inducing DNA lesions to understand DNA damage response in normal and tumoral B-cells. This work is also an opportunity to study in-depth the LSR mechanism since its physiological function has not yet been elucidated.

Associated staff:
Kenza Guiyedi (Master 2)
Israa Al Jamal (PhD student)
Hend Boutouil (PhD, 2015-2018)
Nathalie Gachard (Hospital practitioner ; Biological Hematology Department)
David Rizzo (professor assistant – hospital practitioner ; Biological Hematology Department)
Jasmine Chauzeix (professor assistant – hospital practitioner ; Biological Hematology Department)

 

Availability

CSReport software (Boyer et al. , J Immunol. 2017) enables the analysis of high-throughput sequencing data of PCR products amplifying the recombination junctions of the IgH locus.
CSReport requires the Python3 and Jupyter environments (preferably from an Anaconda distribution) with an updated Biopython package.
CSReport works with a custom reference (derived from NCBI sources) of a constant IgH locus sequence and annotations for humans or mice. The reference should be chosen according to the model organism.
The CSReport notebook file (ZIP archive) including the reference files is available on request by mail.

 

Collaborations

– Cyril Broccardo, CRCT Toulouse
– Patrick Eldin, IRIM Montpellier
– Saïd Aoufouchi, Institut Gustave Roussy, Villejuif

 

Training

Since 2013 : course “Molecular mechanisms of the genetic rearrangements of immunoglobulin genes” in the Immunology-Hematology-Oncology Unit, MASTER 2 Biology-Health – Molecular Oncology and Biotherapies, Faculty of Sciences of Limoges.

 

Education

Since 2013 : permanent researcher INSERM in UMR CNRS 7276 INSERM 1262 « Contrôle de la réponse immune B et des lymphoproliférations » (CRIBL) (Director : Pr. M. Cogné), Limoges.
2009-2013 : Post-doctoral researcher in UMR CNRS 7276 (CRIBL).
2004-2008 : PhD student in Immunology, Université Paris VII et Inserm U768 (Director : Pr A. Fischer), Hôpital Necker, Paris.
thesis topic:  “Molecular characterization of inherited immunoglobulin class switch recombination deficiencies”, Director : Dr. Anne Durandy.
2003-2004 : DEA in extensive immunology, University Paris VI and Institut Pasteur, Paris.
1999-2003 : DEUG SVT then License and Masters in biochemistry, specialty immunology and microbial biochemistry, University of Poitiers.

 

Publications

Eldin P, Péron S, Galashevskaya A, Denis-Lagache N, Cogné M, Slupphaug G and Briant L. HIV-1 may evade antibody class switching via Vpr-mediated UNG2 degradation in bystander B cells – Journal of Translational Medicine, 2020.

Boutouil H, Boyer F, Cook-Moreau J, Cogné M, Péron S. IgH locus suicide recombination does not depend on NHEJ in contrast to CSR in B cells. Cell Mol Immunol. 2019 Feb;16(2):201-202.

Dalloul I, Boyer F, Dalloul Z, Pignarre A, Caron G, Fest T, Chatonnet F, Delaloy C, Durandy A, Jeannet R, Lereclus E, Boutouil H, Aldigier JC, Péron S, Le Noir S, Cook-Moreau J, Cogné M. Locus suicide recombination actively occurs on the functionally rearranged IgH allele in B-cells from inflamed human lymphoid tissues. PLoS Genet. 2019 Jun 14;15(6).

Cresson C, Péron S, Jamrog L, Rouquié N, Prade N, Dubois M, Hébrard S, Lagarde S, Gerby B, Mancini SJC, Cogné M, Delabesse E, Delpy L, Broccardo C. PAX5A and PAX5B isoforms are both efficient to drive B cell differentiation. Oncotarget. 2018 Aug 28;9(67):32841-32854.

Boyer F, Boutouil H, Dalloul I, Dalloul Z, Cook-Moreau J, Aldigier JC, Carrion C, Herve B, Scaon E, Cogné M, Péron S. CSReport: A New Computational Tool Designed for Automatic Analysis of Class Switch Recombination Junctions Sequenced by High-Throughput Sequencing. J Immunol. 2017 May 15;198(10):4148-4155.

Srour N, Chemin G, Tinguely A, Ashi MO, Oruc Z, Péron S, Sirac C, Cogné M, Delpy L. A plasma cell differentiation quality control ablates B cell clones with biallelic Ig rearrangements and truncated Ig production. J Exp Med. 2016 Jan 11;213(1):109-22.

Laffleur B, Duchez S, Tarte K, Denis-Lagache N, Péron S, Carrion C, Denizot Y, Cogné M. Self-Restrained B Cells Arise following Membrane IgE Expression. Cell Rep. 2015 Feb 17;10(6):900-909.

Laffleur B, Denis-Lagache N, Péron S, Sirac C, Moreau J, Cogné M. AID-induced remodeling of immunoglobulin genes and B cell fate. Oncotarget. 2014 Mar 15;5(5):1118-31.

Péron S, Laffleur B, Denis-Lagache N, Cook-Moreau J, Filloux M, Cogné M. [IgH locus suicide recombination, or when B cells surrender!]. Med Sci (Paris). 2012

Péron S, Laffleur B, Denis-Lagache N, Cook-Moreau J, Tinguely A, Delpy L, Denizot Y, Pinaud E, Cogné M. AID-driven deletion causes immunoglobulin heavy chain locus suicide recombination in B cells. Science. 2012 May 18;336(6083):931-4.

Tinguely A, Chemin G, Péron S, Sirac C, Reynaud S, Cogné M, Delpy L. Cross talk between immunoglobulin heavy-chain transcription and RNA surveillance during B cell development. Mol Cell Biol. 2012 Jan;32(1):107-17.

Pinaud E, Marquet M, Fiancette R, Péron S, Vincent-Fabert C, Denizot Y, Cogné M. The IgH locus 3′ regulatory region: pulling the strings from behind. Adv Immunol. 2011;110:27-70.

Péron S, Metin A, Gardès P, Alyanakian MA, Sheridan E, Kratz CP, Fischer A, Durandy A. Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination. J Exp Med. 2008 Oct 27;205(11):2465-72.

Etzioni A, Ben-Barak A, Peron S, Durandy A. Ataxia-telangiectasia in twins presenting as autosomal recessive hyper-immunoglobulin M syndrome. Isr Med Assoc J. 2007 May;9(5):406-7.

Durandy A, Taubenheim N, Peron S, Fischer A. Pathophysiology of B-cell intrinsic immunoglobulin class switch recombination deficiencies. Adv Immunol. 2007;94:275-306. Review.

Péron S, Pan-Hammarstrom Q, Imai K, Du L, Taubenheim N, Sanal O, Marodi L, Bergelin-Besançon A, Benkerrou M, de Villartay JP, Fischer A, Revy P, Durandy A. A primary immunodeficiency characterized by defective immunoglobulin class switch recombination and impaired DNA repair. J Exp Med. 2007 May 14;204(5):1207-16.

Durandy A, Peron S, Taubenheim N, Fischer A. Activation-induced cytidine deaminase: structure-function relationship as based on the study of mutants. Hum Mutat. 2006 Dec;27(12):1185-91. Review.

Durandy A, Peron S, Fischer A. Hyper-IgM syndromes. Curr Opin Rheumatol. 2006 Jul;18(4):369-76. Review.

Notarangelo LD, Lanzi G, Peron S, Durandy A. Defects of class-switch recombination. J Allergy Clin Immunol. 2006 Apr;117(4):855-64. Review.