A switch from canonical to noncanonical autophagy shapes B cell responses

• Published in: Science (American Association for the Advancement of Science) Vol. 355; no. 6325; pp. 641 - 647
• Main Authors: Martinez-Martin, Nuria, Maldonado, Paula, Gasparrini, Francesca, Frederico, Bruno, Aggarwal, Shweta, Gaya, Mauro, Tsui, Carlson, Burbage, Marianne, Keppler, Selina Jessica, Montaner, Beatriz, Jefferies, Harold B. J., Nair, Usha, Zhao, Yan G., Domart, Marie-Charlotte, Collinson, Lucy, Bruckbauer, Andreas, Tooze, Sharon A., Batista, Facundo D.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 10.02.2017; The American Association for the Advancement of Science
• Subjects: Ablation; Activation; Animals; Autophagy; Autophagy - immunology; B-Lymphocytes - immunology; B-Lymphocytes - virology; Cell activation; Cell culture; Cell differentiation; Computer memory; Differentiation; Differentiation (biology); Down-Regulation; Genetics; Germinal Center - immunology; Germinal Center - virology; Germinal centers; Homeostasis; Imaging; Immune system; Immunological memory; Individualized Instruction; Infections; Lymphocyte Activation; Lymphocyte receptors; Lymphocytes B; Maintenance; Mechanistic Target of Rapamycin Complex 1; Medical innovations; Memory cells; Mice; Mice, Inbred C57BL; Mice, Knockout; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Mitochondria - metabolism; Multiprotein Complexes - metabolism; Pathways; Pharmacology; Rapamycin; Stimulation; Switches; T cell receptors; TOR protein; TOR Serine-Threonine Kinases - metabolism; Viral infections; Virus Diseases - immunology; WD40 Repeats - genetics
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.aal3908

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.