title: Autophagy is dispensable for B-cell development but essential for humoral autoimmune responses.
abstract: To gain new insight into the role of B-cell autophagy, we generated two novel mouse models deficient for the autophagy-related gene (Atg)5, one from the outset pro-B cell stage (Atg5(f/-) Mb1 cre) and the other in mature B cells only (Atg5(f/-) CD21 cre). We show that autophagy is dispensable for pro- to pre-B cell transition, but necessary at a basal level to maintain normal numbers of peripheral B cells. It appears non-essential for B-cell activation under B-cell receptor stimulation but required for their survival after lipopolysaccharide stimulation that drives plasmablast differentiation and for specific IgM production after immunization. Results obtained using Atg5(f/-) CD21 cre × C57BL/6(lpr/lpr) autoimmune-prone mice show that B-cell autophagy is involved in the maintenance of anti-nuclear antibody secretion, elevated number of long-lived plasma cells, and sustains IgG deposits in the kidneys. Thus, treatments specifically targeting autophagy might be beneficial in systemic autoimmune diseases.
authors.affiliation: CNRS, Immunopathology and Therapeutic Chemistry/Laboratory of Excellence MEDALIS, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.
authors.forename: J
authors.initials: J
authors.lastname: Arnold
authors.affiliation: CNRS, Immunopathology and Therapeutic Chemistry/Laboratory of Excellence MEDALIS, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.
authors.forename: D
authors.initials: D
authors.lastname: Murera
authors.affiliation: CNRS, Immunopathology and Therapeutic Chemistry/Laboratory of Excellence MEDALIS, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.
authors.forename: F
authors.initials: F
authors.lastname: Arbogast
authors.affiliation: CNRS, Immunopathology and Therapeutic Chemistry/Laboratory of Excellence MEDALIS, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.
authors.forename: J-D
authors.initials: JD
authors.lastname: Fauny
authors.affiliation: CNRS, Immunopathology and Therapeutic Chemistry/Laboratory of Excellence MEDALIS, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.|University of Strasbourg Institute for Advanced Study, Strasbourg, France.
authors.forename: S
authors.initials: S
authors.lastname: Muller
authors.affiliation: CNRS, Immunopathology and Therapeutic Chemistry/Laboratory of Excellence MEDALIS, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.|University of Strasbourg, Strasbourg, France.
authors.forename: F
authors.initials: F
authors.lastname: Gros
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D001343:Autophagy / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D002478:Cells, Cultured; D051379:Mice; D008810:Mice, Inbred C57BL