; INSERM
During the last 20 years I have been studying the mechanisms controlling normal and pathologic B cells from their generation in the BMto their terminal differentiation as PCs. After my PhD in the lab of Dr. C. Schiff dedicated to the analysis of preB/stromal cell interactions in the BM, I decided to focus my post-doctoral work on the mechanisms regulating B cell activation and how they may be jeopardized in the course of autoimmunity. The 2 main focuses of my postdoctoral work in Pr. K. Smith lab (University of Cambridge, UK) were to understand how natural polymorphisms contribute to autoimmune and inflammatory diseases and to characterize the implication of Bcells and PCs in these pathologies. Armed with these experiences, I started a research group in France in 2014 within the unit directed by Dr. F. Bachelerie (U996, Clamart) with the objective to improve our understanding of the biology of PCs in health and disease. I set up an integrative analysis of PCs including their proteomic profiling, study of their differentiation and migratory behaviour as well as analysis of their heterogeneity at the single cell level. In addition, in collaboration with Dr. K. Balabanian, we showed that Cxcr4 desensitization regulates PC biology and is an essential brake controlling the extrafollicular humoral response. The active collaboration between our groups prompted us to set up and co-direct a new lab since 2019, dedicated to the study of the interplay established between lymphocytes and their microenvironment in the BM (Inserm unit U1160, Institut de Recherche Saint Louis, Paris). We are particularly interested in the complex interactions established within the BM ecosystem between HSCs, PCs and the stroma at steady state and under pathological conditions.
Over the last few years my team showed that signaling through the Cxcr4/Cxcl12 axis regulates the strength and the length of the extrafollicular response. This has led us to interrogate the impact of gain of function mutation of Cxcr4 in a lymphoplasmacytic lymphoma, Waldenstrom macroglobulinemia (WM). We developed a new mouse model bearing both Cxcr4 and MyD88 gain of function mutations that recapitulate some of WM key features. One of our key findings was that both mutations drive the expansion of atypical Bcells (ABC) even before disease onset. In parallel, our studies on human WM patients have led to key discoveries on a subset of patients with increased inflammation. In this presentation I will discuss our clinical and fundamental results.
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