Presentation of axis 3 - BIGReS

B-cell Ig Gene Remodeling Singularities

Summary and objectives of Michel Cogné's research team project “B-cell Ig gene Remodeling Singularities” (BIGReS)

Logo BIGReS The topic if 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, we 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)


Sites for locus suicide recombination in human Ig genes

Sites for locus suicide recombination in human Ig genes