Antibodies in Therapy & Pathology (INSERM UMR 1222): focus on Allergy, Autoimmunity and Immunotherapy Antibodies are key effectors of the immune system. They are responsible for disease induction (autoimmunity, allergy) and can be protecting from or facilitating infections and tumors. Antibodies are secreted by terminally differentiated B cells, plasmablasts and plasma cells. Antibodies do not generally exert by themselves, however, biological functions: these are mainly mediated by antibody receptors (FcRs) and complement component C1q. Aims:
1) Decipher the role of human antibodies, human antibody receptors (FcRs) and the cells expressing them (neutrophils, monocytes/macrophages, platelets, mast cells, basophils), and human complement during therapy and in the induction of pathologies (severe allergy & autoimmunity), using primarily mouse models “humanized” for these components.
2) Establish high-throughput plasma cell screening, analysis and/or sorting using droplet microfluidics technologies to understand the antibody response, repertoire and affinities, and demonstrate the pathogenic nature of antibodies in specific diseases .
3) Develop clinical studies (AUTOIMMUNI-B; NASA; WaspPenIP; ENDOPHEN) to understand how antibodies and their effector functions induce/regulate autoimmune and allergic diseases, and how they develop after vaccination.
4) Develop novel antibody-based therapeutics
Altogether, our research integrating fundamental, clinical and industry-driven approaches, aims at elucidating the role of antibodies, their receptors and the cells expressing them in major disease and therapy models and, hopefully, propose novel therapeutic solutions in antibody-based therapies.
- RECENT HIGHLIGHTS
mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants. Sokal A, et al. Immunity 2021 Dec 14;54(12):2893-2907
- Neutrophil-specific gain-of-function mutations in Nlrp3 promote development of cryopyrin-associated periodic syndrome. J Exp Med. 2021 Oct 4;218(10):e20201466.
- Dual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice.
Nat Commun. 2021 May 11;12(1):2574.
Comment on “Tumor-initiating cells establish an IL-33-TGF-β niche signaling loop to promote cancer progression”. Science. 2021 Apr 9;372(6538):eabf2022.
- High-throughput single-cell activity-based screening and sequencing of antibodies using droplet microfluidics. Gérard A, et al. Nat Biotechnol. 2020 Jun;38(6):715-721
- The anti-IgE mAb omalizumab induces adverse reactions by engaging Fcγ receptors. Balbino B, et al. J Clin Invest. 2020 Mar 2;130(3):1330-1335
- An engineered human Fc domain that behaves like a pH-toggle switch for ultra-long circulation persistence. Lee CH, et al. Nat Commun. 2019 Nov 26.
- An IgG-induced neutrophil activation pathway contributes to human drug-induced anaphylaxis. Jönsson F & de Chaisemartin L, et al. Sci Transl Med. 2019
- Evidence that neutrophils do not promote Echis carinatus venom-induced tissue destruction. Stackowicz J, et al. Nat Commun. 2018
- Platelets expressing IgG receptor FcγRIIA/CD32A determine the severity of experimental anaphylaxis. Beutier H, et al. Sci Immunol. 2018
- Single-cell deep phenotyping of IgG-secreting cells for high-resolution immune monitoring. Eyer K, et al. Nat Biotechnol 2017
- IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions. Lee CH, et al. Nat Immunol 2017
- Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide. Reber LL & Gillis CM, et al. J Exp Med 2017