RRC ID 27882
Author 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.
Title Plasma cells require autophagy for sustainable immunoglobulin production.
Journal Nat Immunol
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.
Volume 14(3)
Pages 298-305
Published 2013-3-1
DOI 10.1038/ni.2524
PII ni.2524
PMID 23354484
MeSH Adenosine Triphosphate Animals Antibody Formation Autophagy* Autophagy-Related Protein 5 B-Lymphocytes / immunology B-Lymphocytes / metabolism* Bone Marrow Cells / immunology Cell Differentiation Endoplasmic Reticulum / genetics Endoplasmic Reticulum Stress / genetics Germinal Center / immunology Homeostasis Immunoglobulins / biosynthesis* Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Knockout Microtubule-Associated Proteins / deficiency Microtubule-Associated Proteins / genetics* Plasma Cells / cytology Plasma Cells / immunology* Plasma Cells / metabolism Positive Regulatory Domain I-Binding Factor 1 Transcription Factors / biosynthesis
IF 20.479
Times Cited 209
Mice RBRC00806