AXIS 3 - BIGReS

B-cell Ig Gene Remodeling Singularities

Michel COGNE

Summary and objectives of Michel Cogné's research team project “B-cell Ig gene Remodeling Singularities” (BIGReS)
 
The topic is this team is B cell immunology and immunopathology and its recent research was specially committed to the analysis of the elements regulating Ig gene transcription and recombination. This brought us to explore the class-specific functions impacted into B cells by AID-mediated expression of switched BCR molecules. With colleagues is Limoges, the studied the role of the IgH 3’RR with regards to AID-mediated remodeling events affecting the locus, boosting IgH transcription in plasma cells, and deregulating oncogenes translocated to the IgH locus, thus participating into lymphomagenesis. Besides developing transgenic, KO and knock-in models, pertinent to B cell immunology and lymphomagenesis, the team is involved into translational research, in collaboration with clinicians.

 
Recent scientific achievements hereby are:
· Exploring the functional role of the conserved palindromic architecture of the IgH 3’RR (Saintamand, Nat Comm 2016; Le Noir, Nucleic Acids Research 2017)
· Showing that AID-targeted S regions are not sufficient for CSR (Bonaud, Nat Comm 2015)
· Using a proprietary knock-in mouse model producing human IgA1 for a model of IgA nephropathy initiation (Oruc Z et al, Journal of the American Society of Nephrology. 2016; Webbe B et al, Journal of the American Society of Nephrology 2019)
· Showing that the process of AID-mediated Locus Suicide Recombination that we initially discovered in mice (with BCR loss and consecutive B cell apoptosis) was also highly active in human (Dalloul I et al, Plos Genet 2019)
· Describing other B-lineage negative selection pathways (Death pathways induced by IgE BCR expression (Laffleur B et al, Cell Reports, 2015) / the “TIE-checkpoint”, a late quality control killing cells producing truncated Ig encoded by non-functional alleles (Srour N et al, J Exp Med 2016)

academic appeal or reputation
« Honor team » from Association pour la Recherche sur le Cancer (ARC) in 2018 and Research Prize of Fondation ALLIANZ / Institut de France (2015).
Invited conference at the 19th Germinal Centre Conference (2017) and the FASEB Summer conference on IgE and Allergy Conference: From Mechanisms to Therapy (2019).
Invited conference at the Henri Kunkel’s Society meeting, New York (2020)
Invited seminar at Genentech, San Francisco (2018)
Member of the scientific committee. 50th meeting of the French Society for Immunology, Paris, 2016 Nov 28-30 (joint meeting French, German & Swiss Immunology Societies)
 
team interactions with socioeconomic environment
1. Recent Granted Patents:
• WO2015001510 (filed 08/01/2015) Cogné M et al: “Transgenic non-human mammal for producing chimeric human immunoglobulin E antibodies”.
• EP20190305716 Delpy et al, METHODS FOR MODULATING IMMUNOGLOBULIN EXPRESSION
• WO2016EP78475 Delpy et al. UTILISATION D'OLIGONUCLEOTIDES ANTISENS POUR PRODUIRE DES IG TRONQUEES PAR SAUT D'EXON POUR LE TRAITEMENT DE MALADIES IMPLIQUANT DES CELLULES DE LA LIGNEE B
PCT/EP2019/060764, Cogné M et al: IgG5, a new class of human IgG, application FR1853681 18/04/2018 (Université de Limoges);
•  WO2019EP55453 Cogné M et al: Recombinant single chain immunoglobulins.
2. Industrial partnership:
3 yr-collaboration with AREVA-Med (Orano-Med) for the “CARAT” project corresponding to pre-clinical evaluation of a-radioimmunotherapy (using 212Pb) (2M€ over 3 yrs for the team in Limoges)
3. Cultural institution:  
Online publications for The Conversation
 
team contributions to training actions
1. 5 doctoral students have defended their PhD during the evaluation period, 3 are ongoing PhD students.
2. Teaching in Master courses  (Immunology / Genetics / Oncology) in Limoges, Rennes, Paris and Lyon.