Plasma cells require autophagy for sustainable immunoglobulin production

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)298-305
Number of pages8
JournalNature Immunology
Volume14
Issue number3
DOIs
Publication statusPublished - Mar 2013

ASJC Scopus subject areas

  • Immunology

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    Pengo, N., Scolari, M., Oliva, L., Milan, E., Mainoldi, F., Raimondi, A., Fagioli, C., Merlini, A., Mariani, E., Pasqualetto, E., Orfanelli, U., Ponzoni, M., Sitia, R., Casola, S., & Cenci, S. (2013). Plasma cells require autophagy for sustainable immunoglobulin production. Nature Immunology, 14(3), 298-305. https://doi.org/10.1038/ni2524