A switch from canonical to noncanonical autophagy shapes B cell responses.

Autor: Martinez-Martin N; Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. fbatista1@mgh.harvard.edu nuria.martinezmartin@crick.ac.uk sharon.tooze@crick.ac.uk., Maldonado P; Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Gasparrini F; Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Frederico B; Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Aggarwal S; Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Gaya M; Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Tsui C; Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Burbage M; Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Keppler SJ; Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Montaner B; Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Jefferies HB; Molecular Cell Biology of Autophagy Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Nair U; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA., Zhao YG; Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China., Domart MC; Electron Microscopy Unit, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Collinson L; Electron Microscopy Unit, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Bruckbauer A; Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Tooze SA; Molecular Cell Biology of Autophagy Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. fbatista1@mgh.harvard.edu nuria.martinezmartin@crick.ac.uk sharon.tooze@crick.ac.uk., Batista FD; Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. fbatista1@mgh.harvard.edu nuria.martinezmartin@crick.ac.uk sharon.tooze@crick.ac.uk.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2017 Feb 10; Vol. 355 (6325), pp. 641-647.
DOI: 10.1126/science.aal3908
Abstrakt: Autophagy is important in a variety of cellular and pathophysiological situations; however, its role in immune responses remains elusive. Here, we show that among B cells, germinal center (GC) cells exhibited the highest rate of autophagy during viral infection. In contrast to mechanistic target of rapamycin complex 1-dependent canonical autophagy, GC B cell autophagy occurred predominantly through a noncanonical pathway. B cell stimulation was sufficient to down-regulate canonical autophagy transiently while triggering noncanonical autophagy. Genetic ablation of WD repeat domain, phosphoinositide-interacting protein 2 in B cells alone enhanced this noncanonical autophagy, resulting in changes of mitochondrial homeostasis and alterations in GC and antibody-secreting cells. Thus, B cell activation prompts a temporal switch from canonical to noncanonical autophagy that is important in controlling B cell differentiation and fate.
(Copyright © 2017, American Association for the Advancement of Science.)
Databáze: MEDLINE
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