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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Martinez-Martin, N; Maldonado, P; Gasparrini, F; Frederico, B; Aggarwal, S; Gaya, M; Tsui, C; Burbage, M; Keppler, SJ; Montaner, B; Jefferies, HB; Nair, U; Zhao, YG; Domart, MC; Collinson, L; Bruckbauer, A; Tooze, SA; Batista, FD.
A switch from canonical to noncanonical autophagy shapes B cell responses.
Science. 2017; 355(6325): 641-647.
Doi: 10.1126/science.aal3908
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- Co-authors Med Uni Graz
- Keppler Selina Jessica
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Autophagy - immunology
- B-Lymphocytes - immunology, virology
- Down-Regulation - administration & dosage
- Germinal Center - immunology, virology
- Lymphocyte Activation - administration & dosage
- Mechanistic Target of Rapamycin Complex 1 - administration & dosage
- Mice - administration & dosage
- Mice, Inbred C57BL - administration & dosage
- Mice, Knockout - administration & dosage
- Microtubule-Associated Proteins - genetics, metabolism
- Mitochondria - metabolism
- Multiprotein Complexes - metabolism
- TOR Serine-Threonine Kinases - metabolism
- Virus Diseases - immunology
- WD40 Repeats - genetics