Publication Highlights: Articles on autophagy research published by french laboratories and selected by CFATG.
ATG5 in B cell polarization and antigen presentation
B cells are central actors of the humoral response. Autophagy is implicated in the maintenance of long-lived B cells like antibody-secreting plasma cells and memory B cells. Autophagic activity also allows the presentation of cytosolic antigens by major histocompatibility complex class II (MHC-II) molecules. Antigen presentation is crucial for the crosstalk with T cells, contributing to the terminal differentiation of B cells. Some antigens are presented after capture by the B cell receptor (BCR), the membrane-bound version of the antibody ultimately secreted by plasma cells. The role of autophagy in the presentation of such antigens is suspected but not well understood.
Our work shows that ATG5 (autophagy-related 5) allows the colocalization of the BCR with LC3 and ATG16L1 after internalization. Although autophagic machinery is not necessary for the endocytosis of BCR/antigen complexes, ATG5 allows the relocalization of the centrosome at the vicinity of the place where antigen is first internalized and then processed on MHC-II molecules. ATG5 and ATG16L1 are part of a complex comprising PCM1 (pericentriolar material 1), which expression also participates in this phenomenon.
This polarization of B cells is major when antigen is immobilized on solid phase, mimicking its availability at the membrane of cells in the follicles of secondary lymphoid organs. In this context, ATG5 optimizes B cell presentation by MHC-II molecules to T cells and thus allows a more effective humoral response.
We are currently investigating the interactions between ATG proteins and centrosome components, that promote the reorganization of B cell cytoskeleton, the loading of antigens on MHC-II, and the optimization of the immune response.
The autophagic proteins GABARAP/LGG-1 and LC3/LGG-2 possess specific functions in the exposure of phosphatidylserine and the degradation of apoptotic cells.
Autophagy. 2018 Sep 10:1-14. doi: 10.1080/15548627.2018.1512452.
Autophagy, which means self-eating, is a mechanism for degrading and recycling of cellular constituents. Double membrane vesicles called autophagosomes sequester cytoplasmic material and then fuse with lysosomes that digest their contents. This process is involved in development, longevity and cell death. Autophagy interacts strongly with a cell death program called apoptosis. Following its apoptosis, the cell is phagocytosed by the phagocytic cells forming a phagosome which then fuse with lysosomes causing its degradation (Figure). This process is called phagocytosis of apoptotic bodies.
Using the model animal Caenorhabditis elegans, Renaud Legouis’s laboratory has identified the existence of new functions of autophagy that participate in the phagocytosis of apoptotic bodies. Using genetic and cellular approaches, such as light and electron microscopy, the authors have shown that the autophagic proteins LGG-1 and LGG-2, homologs of the human proteins GABARAP and LC3, play specific roles in the degradation of apoptotic cells. The LGG-1 protein is involved in the exposure at the surface of apoptotic cell of the lipid phosphatidylserine, serving as a death signal and causing its recognition by the phagocytic cell. The LGG-2 protein is specifically required later in the process to allow the maturation and degradation of the phagosome.
The results of this study show the existence of several levels of interactions between autophagy and apoptosis. Understanding these relationships is important at the medical level because manipulating autophagy is a therapeutic issue under study in various human pathologies such as cancers or neurodegenerative diseases.