A switch from canonical to noncanonical autophagy shapes B cell responsesMore about Open Access at the Crick
Authors listNuria Martinez-Martin Paula Maldonado Francesca Gasparrini Bruno Goncalves Frederico Shweta Aggarwal Mauro Gaya Carlson Tsui Marianne Burbage Selina Jessica Keppler Beatriz Montaner Harold Jefferies Usha Nair Yan G Zhao Marie-Charlotte Domart Lucy Collinson Andreas Bruckbauer Sharon 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.
Issue number 6325