Autophagy is dispensable for B-cell development but essential for humoral autoimmune responses
In: Cell Death & Differentiation, Jg. 23 (2015-11-20), S. 853-864
Online
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Zugriff:
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.
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Autophagy is dispensable for B-cell development but essential for humoral autoimmune responses
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Autor/in / Beteiligte Person: | Muller, Sylviane ; Fauny, Jean-Daniel ; Arbogast, Florent ; Arnold, Johan ; Gros, Frédéric ; Murera, Diane ; Immunopathologie et chimie thérapeutique (ICT) ; Institut de biologie moléculaire et cellulaire (IBMC) ; Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) ; Biotechnologie et signalisation cellulaire (BSC) ; Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS) |
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Zeitschrift: | Cell Death & Differentiation, Jg. 23 (2015-11-20), S. 853-864 |
Veröffentlichung: | Springer Science and Business Media LLC, 2015 |
Medientyp: | unknown |
ISSN: | 1476-5403 (print) ; 1350-9047 (print) |
DOI: | 10.1038/cdd.2015.149 |
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