Research
During my master and PhD studies in France (in Michel Cogné’s laboratory, CNRS UMR7276 CRIBL, Limoges, with Yves Denizot), I studied a master transcriptional enhancer laying at the very end of the immunoglobulins heavy chain locus (IgH), downstream of the gene segments encoding the switchable constant region of the antibodies. This complex locus control region, the 3’ regulatory region (IgH 3’RR) exhibits a versatile ‘half-angel, half-devil’ behaviour. This region is essential to drive the genomic rearrangements occurring during somatic hypermutation and class switch recombination, when B cells adjust not only their antigen affinity but also their effector function, during the late phase of their maturation. The remarkable plasticity of the B cells to engage the most adapted and powerful protection and fight an infection as efficiently as possible relies on the inherent genomic instability of the IgH locus. Although absolutely necessary for the adaptive B cell response, the IgH 3’RR can be detrimental in some circumstances and trigger pathologic conditions. Indeed, the counterpart of this physiological and beneficial function is the recurrent and excessive activation of proto-oncogenes inserted into or juxtaposed to the IgH locus after oncogenic translocations, detected in most of B-cell lymphomas. Since the IgH locus is naturally prone to gene rearrangements, it is de facto a frequent fusion partner for oncogene translocations (e.g. c-myc in Burkitt lymphoma or bcl-2 in follicular lymphoma) […] we investigated the physiological and pathological functions of the IgH 3’RR with different mouse models (transgenic and knocked-out).
In 2011, I moved to Cambridge (MRC-LMB) to join the Alex Betz’ group, studying the initiation and regulation of immune responses, where I have embarked on projects involving the second branch of the adaptive immune system: T cells. I am particularly interested in CD4 T cell memory, investigating its generation, function and maintenance. Immunological memory is the hallmark of adaptive immunity. It relates to its ability to remember a primary response and induce a faster secondary response with a higher magnitude to face a re-exposure to the same antigen. During the course of an immune response, memory lymphocytes survive the so-called ‘contraction phase’, when most of the effector immune cells are cleared to avoid a prolonged immune reaction (potentially deleterious for the surrounding tissues).
Current supervisor: Dr. Alex G. Betz
Collaborators:
- Dr. David R. Withers, School of Infection and Immunity, University of Birmingham.
- Prof. Tim Sparwasser, TWINCORE – Institute of Infection Immunology – Hannover Medical School.
Publications
Rouaud P., Vincent-Fabert C., Saintamand A., Fiancette R., Marquet M., Robert I., Reina-San-Martin B., Pinaud E., Cogné M. and Denizot Y., 2013, The IgH 3' regulatory region controls somatic hypermutation in germinal center B cells. J. Exp. Med. 210(8): 1501-1507.
Rouaud P., Fiancette R., Vincent-Fabert C., Magnone V., Cogné M., Dubus P. and Denizot Y., 2012, Mantle cell lymphoma-like lymphomas in c-myc-3'RR/p53+/- mice and c-myc-3'RR/Cdk4R24C mice: differential oncogenic mechanisms but similar cellular origin. Oncotarget 3(5): 586-593.
Vincent-Fabert C., Fiancette R.*, Rouaud P.*, Baudet C., Truffinet V., Magnone V., Guillaudeau A., Cogné M., Dubus P. and Denizot Y., 2012, A Defect of the INK4-Cdk4 Checkpoint and Myc Collaborate in Blastoid Mantle Cell Lymphoma-Like Lymphoma Formation in Mice. Am. J. Pathol. 180(4):1688-1701.
Rouaud P.*, Vincent-Fabert C.*, Fiancette R., Cogné M., Pinaud E. and Denizot Y., 2012, Enhancers Located in Heavy Chain Regulatory Region (hs3a, hs1,2, hs3b, and hs4) Are Dispensable for Diversity of VDJ Recombination. J. Biol. Chem. 287(11): 8356-8360.
Fiancette R., Rouaud P., Vincent-Fabert C., Laffleur B. Magnone V., Cogné M. and Denizot Y., 2011, A p53 defect sensitizes various stages of B cell development to lymphomagenesis in mice carrying an IgH 3’ regulatory region-driven c-myc transgene. J. Immunol. 187(11): 5772-5782.
Vincent-Fabert C., Fiancette R., Pinaud E., Truffinet V., Cogné N., Cogné M. and Denizot Y., 2010, Genomic deletion of the whole IgH 3' regulatory region (hs3a, hs1,2, hs3b, hs4) dramatically affects class switch recombination and Ig secretion to all isotypes. Blood 116(11):1895-1898.
Fiancette R., Amin R., Truffinet V., Vincent-Fabert C., Cogné N., Cogné M. and Denizot Y., 2010, A myeloma translocation-like model associating CCND1 with the immunoglobulin heavy-chain locus 3' enhancers does not promote by itself B-cell malignancies. Leuk. Res. 34(8): 1043-1051.
Vincent-Fabert C., Fiancette R., Truffinet V., Cogné N., Cogné M. and Denizot Y., 2009, Genetic background modulates susceptibility to oncogen-driven proliferation and lymphoma occurrence in mice carrying a deregulated c-myc transgene. Leuk. Res. 33(11): e203-e206.
Vincent-Fabert C.*, Truffinet V.*, Fiancette R., Cogné N., Cogné M. and Denizot Y., 2009, Ig synthesis and class switching do not require the presence of the hs4 enhancer in the 3' IgH regulatory region. J. Immunol. 182(11): 6926-6932.
Vincent C.*, Truffinet V.*, Fiancette R., Petit B., Cogné N., Cogné M. and Denizot Y., 2009, Uncoupling between Ig somatic hypermutation and oncogene mutation in mouse lymphoma. Biochimica and Biophysica Acta – Molecular Cell Research 1793(2): 418-426.
Pinaud E., Marquet M., Fiancette R., Péron S., Vincent-Fabert C., Denizot Y. and Cogné M., 2011, The IgH locus 3’ regulatory region: pulling the strings from behind. Adv. Immunol. 110: 27-70. DOI: 10.1016/B978-0-12-387663-8.00002-8.
Vincent-Fabert C.*, Fiancette R.*, Cogné M., Pinaud E. and Denizot Y., 2010, The IgH 3’ regulatory region and its implication in lymphomagenesis. Eur. J. Immunol. 40(12): 3306-3311. DOI: 10.1002/eji.201040778.
