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A switch from canonical to noncanonical autophagy shapes B cell responses

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posted on 28.10.2020, 14:04 by Nuria Martinez-Martin, Paula Maldonado, Francesca Gasparrini, Bruno Frederico, Shweta Aggarwal, Mauro Gaya, Carlson Tsui, Marianne Burbage, Selina Jessica Keppler, Beatriz Montaner, Harold BJ Jefferies, Usha Nair, Yan G Zhao, Marie-Charlotte Domart, Lucy Collinson, Andreas Bruckbauer, Sharon A Tooze, Facundo D Batista
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.

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