Autoimmune and B Cells Immune Responses – AI2B
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:
- Why do some individuals develop autoimmune disorders? And are there unique cellular and molecular basis for autoimmune B cell responses?
- How and when do we maintain memory B cells and plasma cells for decades, what is their niche 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 (ANR BREAK-ITP, ERC DIPP IMMUNE). Simultaneously, our group is part of national and international consortia (RHU COVIFERON, H2020 UNDINE) 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. Using these models, we now aim to elucidate the mechanisms governing the settlement of memory B cells and long-lived plasma cells within splenic and bone marrow niches (ANR DECODE-MEMO, ERC DIPP-IMMUNE). Finally, our lab also focuses on B cell responses to emerging viral threats (ANR DECODE-MEMO, PEPR MIE SURVI3) and newly developed vaccines (COVIBOOST clinical trial, H2020 SOLVE) to better understand the underlying determinants of long-lived humoral protection and preexisting memory B cell repertoire remodeling.
Our research is dedicated to unraveling the complexities of immune memory, autoimmunity, and vaccination responses in the context of human health.
France 2030 funding - precisions
ANR funding - precisions
