Document Detail


Plasma cells require autophagy for sustainable immunoglobulin production.
MedLine Citation:
PMID:  23354484     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The role of autophagy in plasma cells is unknown. Here we found notable autophagic activity in both differentiating and long-lived plasma cells and investigated its function through the use of mice with conditional deficiency in the essential autophagic molecule Atg5 in B cells. Atg5(-/-) differentiating plasma cells had a larger endoplasmic reticulum (ER) and more ER stress signaling than did their wild-type counterparts, which led to higher expression of the transcriptional repressor Blimp-1 and immunoglobulins and more antibody secretion. The enhanced immunoglobulin synthesis was associated with less intracellular ATP and more death of mutant plasma cells, which identified an unsuspected autophagy-dependent cytoprotective trade-off between immunoglobulin synthesis and viability. In vivo, mice with conditional deficiency in Atg5 in B cells had defective antibody responses, complete selection in the bone marrow for plasma cells that escaped Atg5 deletion and fewer antigen-specific long-lived bone marrow plasma cells than did wild-type mice, despite having normal germinal center responses. Thus, autophagy is specifically required for plasma cell homeostasis and long-lived humoral immunity.
Authors:
Niccolò Pengo; Maria Scolari; Laura Oliva; Enrico Milan; Federica Mainoldi; Andrea Raimondi; Claudio Fagioli; Arianna Merlini; Elisabetta Mariani; Elena Pasqualetto; Ugo Orfanelli; Maurilio Ponzoni; Roberto Sitia; Stefano Casola; Simone Cenci
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-27
Journal Detail:
Title:  Nature immunology     Volume:  -     ISSN:  1529-2916     ISO Abbreviation:  Nat. Immunol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100941354     Medline TA:  Nat Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1] Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy. [2] Università Vita-Salute San Raffaele, Milano, Italy.
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