| Plasma cells require autophagy for sustainable immunoglobulin production. | |
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MedLine Citation:
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PMID: 23354484 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2013-1-27 |
Journal Detail:
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Title: Nature immunology Volume: - ISSN: 1529-2916 ISO Abbreviation: Nat. Immunol. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100941354 Medline TA: Nat Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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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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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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