Séminaire CIRI (27.02.2025): Frédéric GROS

Frédéric GROS, UMR 1109 INSERM/Université de Strasbourg, Groupe Homéostasie Lymphocytaire et Autoimmunité (Pr Soulas-Sprauel), "Autophagy-related proteins in B cell receptor trafficking and antigen presentation"

Abstract: Autophagy-related proteins play several roles aside the execution of macroautophagy itself. Some of them have been involved in trafficking events such as endocytosis or phagocytosis. Our group identified in primary B cells, the importance of the core autophagy protein ATG5, in B cell receptor trafficking after its internalization triggered by a surrogate antigen. ATG5 is necessary to relocalize the centrosome at the vicinity of the immune synapse engaged by the BCR with a particle, covered with antigens. ATG5 allows then the maintenance of a polarized endocytosis, necessary to optimize antigen presentation to cognate T cells. To decipher the mechanisms in which ATG proteins are involved, we intended to identify partners of ATG proteins enriched after BCR engagement. Using the B cell line BJAB, we first validated ATG16L1 as necessary for BCR polarization. Generating ATG16L1-tagged cell lines for quantitative proteomic approaches, we were able to identify the protein SNAP23 (synaptosome-associated protein of 23 KDa) as an ATG16L1 partner enriched during BCR engagement. We then observed that deletion of SNAP23 impacted the transit of endocytosed BCR towards LAMP1 positive compartments. We thus think that during synapse formation, ATG proteins facilitate the transfer from the plasma membrane towards lysosomes, through its interaction with SNAP23. We are now investigating the consequences of SNAP23 deletion on MHC-II peptide processing and presentation to cognate T cells. In parallel we generated an in vivo model with B cells expressing a BCR specific for the model antigen HEL (Hen egg lysosomes), together with a deficiency for the protein ATG5. This model will allow us to precisely define the consequences of autophagy deficiency in the optimization of antigen presentation, at the germinal center phase, where the antigen is acquired by B cells. This work will lead to a better comprehension of the fine tuning of the GC response by ATG proteins after stimulation with particulate antigens.