Chargé de recherche classe normale INSERM
Équipe B-NATION
We explore how the molecular machineries of DNA and RNA shape the life of B lymphocytes.
We investigate how genome organization, DNA recombination, and RNA regulation guide B cells from activation to antibody secretion, and how failures in these processes lead to B cell malignancies.
Bureau 107 CBRS 05 19 56 42 04
Recherche
DyNAB “Dynamics of Nucleic Acids in B cells”
The immune system relies on B lymphocytes to generate highly specific and long-lasting antibody responses. Upon activation, B cells undergo profound molecular and cellular transformations, including rapid proliferation, immunoglobulin class switch recombination, affinity maturation, and differentiation into antibody-secreting plasma cells.
Our research aims to understand how DNA- and RNA-based regulatory mechanisms coordinate these fundamental processes. We investigate how genome organization, DNA recombination, DNA repair, transcriptional regulation, and RNA modifications shape B cell activation and fate decisions.
A major focus of the group is the study of programmed DNA alterations that occur during antibody diversification. These processes require the generation and repair of DNA lesions within a highly dynamic nuclear environment. We seek to understand how nuclear architecture contributes to genome stability while enabling the genetic plasticity required for adaptive immunity and antibody production.
In parallel, we explore emerging roles of RNA processing and epitranscriptomic regulation in B cell biology.
By studying the interplay between DNA and RNA regulatory networks, we aim to uncover novel mechanisms that control physiologic lymphocyte differentiation and prevent pathologic lymphoproliferative disorders.
Through an integrative approach combining cellular and molecular biology, genomics, bioinformatics, and functional studies, our work seeks to decipher the nucleic acid-based mechanisms that govern B cell function in health and disease in humans.
Publications
Miglierina E, Bouder J, Ordanoska D, Pineau M, Léonard S, Schavgoulidze A, Quéré G, Le Goff M, Bouchet M, Genebrier S, Bastos Serra Trinca S, Deleurme L, Monvoisin C, Derrier L, Dumontet C, Delpy L, Moreaux J, Corre J, Cogné M, Laffleur B
DIS3 licenses B cells for plasma cell differentiation in humans
Cellular and Molecular Immunology 2025
Miglierina E, Ordanoska D, Le Noir S, Laffleur B
RNA processing mechanisms contribute to genome organization and stability in B cells
Oncogene 2024
Laffleur B, Batista CR, Zhang W, Lim J, Yang B, Rossille D, Wu L, Estrella J, Rothschild G, Pefanis E, Basu U
RNA exosome drives early B cell development via noncoding RNA processing mechanisms
Science Immunology 2022
Arrieta VA, Chen AX, Kane JR, Kang SJ, Kassab C, Dmello C, Zhao J, Burdett KB, Upadhyayula PS, Lee-Chang C, Shilati J, Jaishankar D, Chen L, Gould A, Zhang D, Yuan J, Zhao W, Ling X, Burks JK, Laffleur B, Amidei C, Bruce JN, Lukas RV, Yamaguchi JT, Cieremans D, Rothschild G, Basu U, McCord M, Brat DJ, Zhang H, Cooper LAD, Zhang B, Sims P, Cloughesy TF, Prins R, Canoll P, Stupp R, Heimberger AB, Horbinski C, Iwamoto FM, Rabadan R, Sonabend AM
ERK1/2 phosphorylation predicts survival following anti-PD-1 immunotherapy in recurrent glioblastoma
Nature Cancer 2021
Rogier M, Moritz J, Robert I, Lescale C, Heyer V, Abello A, Martin O, Capitani K, Thomas M, Thomas-Claudepierre AS, Laffleur B, Jouan F, Pinaud E, Tarte K, Cogné M, Conticello SG, Soutoglou E, Deriano L, Reina-San-Martin B
Fam72a enforces error-prone DNA repair during antibody diversification
Nature 2021
Marchalot A, Horiot C, Lambert JM, Carrion C, Oblet C, Pollet J, Cogné M, Moreau J, Laffleur B, Delpy L
Targeting IgE polyadenylation signal with antisense oligonucleotides decreases IgE secretion and plasma cell viability
The Journal of Allergy and Clinical Immunology 2021
Nair L, Zhang W, Laffleur B, Jha MK, Lim J, Lee H, Wu L, Alvarez NS, Liu ZP, Munteanu EL, Swayne T, Hanna JH, Ding L, Rothschild G, Basu U
Mechanism of noncoding RNA-associated N6-methyladenosine recognition by an RNA processing complex during IgH DNA recombination
Molecular Cell 2021
Laffleur B, Lim J, Zhang W, Chen Y, Pefanis E, Bizarro J, Batista C, Wu L, Economides A, Wang J, Basu U
Noncoding RNA processing by DIS3 regulates chromosomal architecture and somatic hypermutation in B cells
Nature Genetics 2021
Kazadi D, Lim J, Rothschild G, Grinstein V, Laffleur B, Becherel O, Lavin MJ, Basu U
Effects of senataxin and RNA exosome on B-cell chromosomal integrity
Heliyon 2020
Rothschild G, Zhang W, Lim J, Laffleur B, Chen Y, Fang M, Giri P, Chen Y, Nair L, Liu ZP, Deng H, Hammarström L, Wang J, Basu U
Noncoding RNA transcription alters chromosomal topology to promote isotype specific class switch recombination
Science Immunology 2020
Laffleur B, Basu U
Biology of RNA Surveillance in Development and Disease
Trends in Cell Biology 2019
Laffleur B, Debeaupuis O, Dalloul Z, Cogné M
B Cell Intrinsic Mechanisms Constraining IgE Memory
Frontiers in Immunology 2017
Rialdi A, Hultquist J, Jimenez-Morales D, Peralta Z, Campisi L, Fenouil R, Moshkina N, Wang ZZ, Laffleur B, Kaake RM, McGregor MJ, Haas K, Pefanis E, Albrecht RA, Pache L, Chanda S, Jen J, Ochando J, Byun M, Basu U, García-Sastre A, Krogan N, van Bakel H, Marazzi I
The RNA Exosome Syncs IAV-RNAPII Transcription to Promote Viral Ribogenesis and Infectivity
Cell 2017
Lim J, Giri PK, Kazadi D, Laffleur B, Zhang W, Grinstein V, Pefanis E, Brown LM, Ladewig E, Martin O, Chen Y, Rabadan R, Boyer F, Rothschild G, Cogné M, Pinaud E, Deng H, Basu U
Nuclear Proximity of Mtr4 to RNA Exosome Restricts DNA Mutational Asymmetry
Cell 2017
Le Noir S, Laffleur B, Carrion C, Garot A, Lecardeur S, Pinaud E, Denizot Y, Skok J, Cogné M
The IgH locus 3’ cis-regulatory super-enhancer co-opts AID for allelic transvection
Oncotarget 2017
Laffleur B, Basu U, Lim J
RNA exosome and Non-coding RNA coupled mechanisms in AID mediated genomic alterations
Journal of Molecular Biology 2017
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 Reports 2015
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
Laffleur B, Bardet SM, Garot A, Brousse M, Baylet A, Cogné M
Immunoglobulin genes undergo legitimate repair in human B cells not only after cis- but also frequent trans-class switch recombination
Genes and Immunity 2014
Pascal V, Laffleur B, Debin A, Cuvillier A, Van Egmond M, Drocourt D, Imbertie L, Pangault C, Tarte K, Tiraby G, Cogné M
Anti-CD20 IgA can protect mice against lymphoma development: evaluation of the direct impact of IgA and cytotoxic effector recruitment on CD20 target cells
Haematologica 2012
Péron S, Laffleur B, Denis-Lagache N, 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