Welcome on the Necker-Enfants Malades Institute website
Matthieu Mahévas is a physician-researcher in the French reference center for immune thrombocytopenia at Henri-Mondor Hospital (CERECAI). He did his PhD in the lab of Claude-Agnès Reynaud and Jean-Claude Weill at Institut Necker-Enfants Malades (INEM), during which he demonstrated that B cell-depletion therapy favors the emergence of splenic long-lived pathogenic plasma cells. Named MCU-PH in 2014 and PU-PH at the Faculté de Médecine de l’Université Paris-Est Créteil in 2019, he has been awarded an ATIP/Avenir grant in 2022 and is since 2023 the head of the group “Auto-immune and immune B cells (AI2B)” at Institut Necker Enfants Malades where he pursues is early clinical and scientific research interests focused on understanding the cellular and molecular mechanisms of auto-immune disease and on developing innovative therapies, with numerous past and ongoing clinical trials (RITUX-PLUS, RITUX-PLUS2, IVIORDEX, STOPAGO). More recently, his group also used its unique expertise at studying human B cells at the single cell level to provide seminal work on the maturation of memory B cells after SARS-CoV-2 infection or mRNA vaccination. He has been elected as a fellow of the Henri Kunkel Society in 2021.
Our group investigates the underlying mechanisms, cellular populations involved and fundamental steps leading to the tolerance breakdown in B cells and the establishment of a long-lived immune memory in normal and pathologic context in Human.
Both plasma cells and long-lived memory B cells have been shown to participate in long-term protection against pathogens. And the most effective vaccines can induce a lifelong memory response in immunized individuals, as is the case with smallpox or yellow fever vaccination.
However, B cells and plasma cells targeting self-antigens have also been highlighted as key players in the development of numerous autoimmune diseases, including immune thrombocytopenia (ITP), or severe form of COVID-19. Our laboratory focuses on two central questions in immunology:
Our first objective in the lab aims at addressing the fundamental question of tolerance breakdown in Human from two independent angles. Using first a unique access to splenic samples from immune thrombocytopenia (ITP) patients at different stage in the disease and with likely different etiologies, we aim to draw upon our previous work in ITP, a prototypical B cell mediated auto-immune disease, to explore the underlying cause(s) of tolerance breakdown in B cells and define the pathogenic program of auto-immune plasma cells, key actors of the auto-immune response. In parallel to this, our group is also part of a national consortium (RHU COFIFERON) aiming in part at better understanding the origin of anti-Type I IFN antibodies in older adults, auto-antibodies notably at the basis of severe forms of COVID-19.
A second major focus in the lab has been to decipher the cellular mechanisms involved in memory B cell generation and longevity. The SARS-CoV-2 pandemic and the subsequent worldwide vaccination campaign has provided us with a perfect physiological “model” to describe the early steps of a response to a neo-viral antigen in human. We also recently took advantage of the unique setting provided by smallpox eradication in the late 1970s to perform the first functional analysis of 50 years old resting memory B cells in Human. We are now building upon these works to 1) decipher the role of antigen imprinting in shaping B cell memory to drifted SARS-CoV2 variants both in the context of breakthrough infections or variant-based vaccine development, 2) address the separate question of the functional longevity of such response through the analysis of SARS-CoV-2-specific memory B cells and plasma cells seeding in known niches of long-lasting immune cells as well as through the analysis of the recruitment of decades old vaccinia-generated memory B cells in the recent Monkeypox outbreak and subsequent MVA vaccination campaign.
