title: ATG5 regulates plasma cell differentiation.
abstract: Autophagy is a conserved homeostatic process in which cytoplasmic contents are degraded and recycled. Two ubiquitin-like conjugation pathways are required for the generation of autophagosomes, and ATG5 is necessary for both of these processes. Studies of mice deficient in ATG5 reveal a key role for autophagy in T lymphocyte function, as well as in B cell development and B-1a B cell maintenance. However, the role of autophagy genes in B cell function and antibody production has not been described. Using mice in which Atg5 is conditionally deleted in B lymphocytes, we showed here that this autophagy gene is essential for plasma cell homeostasis. In the absence of B cell ATG5 expression, antibody responses were significantly diminished during antigen-specific immunization, parasitic infection and mucosal inflammation. Atg5-deficient B cells maintained the ability to produce immunoglobulin and undergo class-switch recombination, yet had impaired SDC1 expression, significantly decreased antibody secretion in response to toll-like receptor ligands, and an inability to upregulate plasma cell transcription factors. These results build upon previous data demonstrating a role for ATG5 in early B cell development, illustrating its importance in late B cell activation and subsequent plasma cell differentiation.
authors: Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors: Kara L
authors: KL
authors: Conway
authors: Petric
authors: P
authors: Kuballa
authors: Bernard
authors: B
authors: Khor
authors: Mei
authors: M
authors: Zhang
authors: Hai Ning
authors: HN
authors: Shi
authors: Herbert W
authors: HW
authors: Virgin
authors: Ramnik J
authors: RJ
authors: Xavier
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000941:Antigens / Q000276:immunology; D000071187:Autophagy-Related Protein 5; D002454:Cell Differentiation / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007422:Intestines / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D018655:Lymphocyte Count; D008221:Lymphoid Tissue / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000378:metabolism*; D009351:Nematospiroides dubius / Q000276:immunology; D010537:Peritoneum / Q000166:cytology; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D000941:Antigens; C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D000939:Epitopes; D008869:Microtubule-Associated Proteins
keywords: ATG5; B lymphocytes; antibody secretion; immunity; plasma cell differentiation