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Autoimmune and B cells immune responses

Matthieu Mahévas
Team description

Our research group delves into the intricate mechanisms underlying the breakdown of tolerance in B cells and the establishment of long-lived immune memory, both in normal and pathological human contexts.

Plasma cells and long-lived memory B cells have emerged as key players in providing long-term protection against pathogens, a phenomenon often observed in the most effective vaccines, such as smallpox or yellow fever vaccination. Conversely, B cells and plasma cells targeting self-antigens have been implicated in the development of various autoimmune diseases, including immune thrombocytopenia and severe forms of COVID-19. Our laboratory is dedicated to addressing two pivotal questions in immunology:

  1. Why do some individuals develop autoimmune disorders?
  2. How and when do we maintain memory B cells for decades, and what are the relationships between long-lived memory B cells and plasma cell generation in humans?

Our research is twofold. We investigate the breakdown of B cell tolerance in human diseases, using unique access to splenic samples from immune thrombocytopenia patients. Simultaneously, our group is part of a national consortium (RHU COFIFERON) working to gain a deeper understanding of the origin of anti-Type I IFN antibodies in older adults, auto-antibodies that underlie severe forms of COVID-19.

The second major focus of our research lab centers on deciphering the cellular mechanisms involved in memory B cell generation and longevity. The SARS-CoV-2 pandemic and the ensuing global vaccination campaign have provided us with a unique opportunity to investigate the early stages of a response to a novel viral antigen in humans. Additionally, we've leveraged the exceptional circumstances surrounding the eradication of smallpox in the late 1970s to conduct the first functional analysis of 50-year-old resting memory B cells in humans

Our research is dedicated to unraveling the complexities of immune memory, autoimmunity, and vaccination responses in the context of human health.

Key publications
Sokal A, Bastard P, Chappert P, Barba-Spaeth G, Fourati S, Vanderberghe A, Lagouge-Roussey P, Meyts I, Gervais A, Bouvier-Alias M, Azzaoui I, Fernández I, de la Selle A, Zhang Q, Bizien L, Pellier I, Linglart A, Rothenbuhler A, Marcoux E, Anxionnat R, Cheikh N, Léger J, Amador-Borrero B, Fouyssac F, Menut V, Goffard JC, Storey C, Demily C, Mallebranche C, Troya J, Pujol A, Zins M, Tiberghien P, Gray PE, McNaughton P, Sullivan A, Peake J, Levy R, Languille L, Rodiguez-Gallego C, Boisson B, Gallien S, Neven B, Michel M, Godeau B, Abel L, Rey FA, Weill JC, Reynaud CA, Tangye SG, Casanova JL, Mahévas M. Human type I IFN deficiency does not impair B cell response to SARS-CoV-2 mRNA vaccination. J Exp Med. 2023; Jan 2;220(1):e20220258. doi: 10.1084/jem.20220258. PMID: 36342455 ; PMCID: PMC9814155.
Chappert P, Huetz F, Espinasse MA, Chatonnet F, Pannetier L, Da Silva L, Goetz C, Mégret J, Sokal A, Crickx E, Nemazanyy I, Jung V, Guerrera C, Storck S, Mahévas M, Cosma A, Revy P, Fest T, Reynaud CA, Weill JC. Human anti-smallpox long-lived memory B cells are defined by dynamic interactions in the splenic niche and long-lasting germinal center imprinting. Immunity. 2022; Oct 11;55(10):1872-1890.e9. doi: 10.1016/j.immuni.2022.08.019. PMID: 36130603 ; PMCID: PMC7613742.
Sokal A, Barba-Spaeth G, Fernández I, Broketa M, Azzaoui I, de La Selle A, Vandenberghe A, Fourati S, Roeser A, Meola A, Bouvier-Alias M, Crickx E, Languille L, Michel M, Godeau B, Gallien S, Melica G, Nguyen Y, Zarrouk V, Canoui-Poitrine F, Pirenne F, Mégret J, Pawlotsky JM, Fillatreau S, Bruhns P, Rey FA, Weill JC, Reynaud CA, Chappert P, Mahévas M. mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants. Immunity. 2021; Dec 14;54(12):2893-2907.e5. doi: 10.1016/j.immuni.2021.09.011. PMID: 34614412 ; PMCID: PMC8452492.
Crickx E, Chappert P, Sokal A, Weller S, Azzaoui I, Vandenberghe A, Bonnard G, Rossi G, Fadeev T, Storck S, Fadlallah J, Meignin V, Rivière E, Audia S, Godeau B, Michel M, Weill JC, Reynaud CA, Mahévas M. Rituximab-resistant splenic memory B cells and newly engaged naive B cells fuel relapses in patients with immune thrombocytopenia. Sci Transl Med. 2021; Apr 14;13(589):eabc3961. doi: 10.1126/scitranslmed.abc3961. PMID: 33853929 ; PMCID: PMC7610758.
Sokal A, Chappert P, Barba-Spaeth G, Roeser A, Fourati S, Azzaoui I, Vandenberghe A, Fernandez I, Meola A, Bouvier-Alias M, Crickx E, Beldi-Ferchiou A, Hue S, Languille L, Michel M, Baloul S, Noizat-Pirenne F, Luka M, Mégret J, Ménager M, Pawlotsky JM, Fillatreau S, Rey FA, Weill JC, Reynaud CA, Mahévas M. Maturation and persistence of the anti-SARS-CoV-2 memory B cell response. Cell. 2021; Mar 4;184(5):1201-1213.e14. doi: 10.1016/j.cell.2021.01.050. PMID: 33571429 ; PMCID: PMC7994111.
Funding and grants