| First Author | Pengo N | Year | 2013 |
| Journal | Nat Immunol | Volume | 14 |
| Issue | 3 | Pages | 298-305 |
| PubMed ID | 23354484 | Mgi Jnum | J:193479 |
| Mgi Id | MGI:5468603 | Doi | 10.1038/ni.2524 |
| Citation | Pengo N, et al. (2013) Plasma cells require autophagy for sustainable immunoglobulin production. Nat Immunol 14(3):298-305 |
| abstractText | 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. |
