A switch from canonical to noncanonical autophagy shapes B cell responses.
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.
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.
Nuria
0000-0003-2309-8920
N
Martinez-Martin
Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Paula
P
Maldonado
Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Francesca
F
Gasparrini
Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Bruno
0000-0002-6985-3090
B
Frederico
Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Shweta
S
Aggarwal
Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Mauro
0000-0002-7535-8678
M
Gaya
Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Carlson
C
Tsui
Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Marianne
0000-0003-0686-2608
M
Burbage
Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Selina Jessica
SJ
Keppler
Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Beatriz
0000-0001-9877-7317
B
Montaner
Molecular Cell Biology of Autophagy Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Harold B J
HB
Jefferies
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
Usha
0000-0002-1927-6889
U
Nair
Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
Yan G
YG
Zhao
Electron Microscopy Unit, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Marie-Charlotte
0000-0002-5703-2922
MC
Domart
Electron Microscopy Unit, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Lucy
0000-0003-0260-613X
L
Collinson
Lymphocyte Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Andreas
0000-0003-1419-9674
A
Bruckbauer
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.
Sharon A
0000-0002-2182-3116
SA
Tooze
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.
Facundo D
0000-0002-1130-9463
FD
Batista
D000818:Animals; D001343:Autophagy / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology*; D015536:Down-Regulation; D018858:Germinal Center / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014777:Virus Diseases / Q000276:immunology*; D000071678:WD40 Repeats / Q000235:genetics
C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases