A switch from canonical to noncanonical autophagy shapes B cell responses

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Science  10 Feb 2017:
Vol. 355, Issue 6325, pp. 641-647
DOI: 10.1126/science.aal3908

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In the immune system, autophagy has been implicated in the maintenance and survival of plasma and memory cells, but its role in B cells during early viral infection remains unclear. Martinez-Martin et al. investigated the role of autophagy in B cells by using a combination of innovative imaging, pharmacological agents, and genetic models. B cell activation triggered an increase in the rate of autophagy and also switched the mechanism from canonical autophagy to noncanonical pathways involving the regulator WIPI2. Genetic ablation of WIPI2 in B cells promoted noncanonical autophagy. WIPI2 restrains noncanonical autophagy upon B cell activation through a mechanism involving mitochondrial status. Thus, the switch from canonical to noncanonical autophagy regulates B cell differentiation and fate during viral infection.

Science, this issue p. 641


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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