Report

A switch from canonical to noncanonical autophagy shapes B cell responses

See allHide authors and affiliations

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

You are currently viewing the abstract.

View Full Text

Change for good

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

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.

View Full Text