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Plasma cells require autophagy for sustainable immunoglobulin production.

Pengo, Niccolò; Scolari, Maria; Oliva, Laura; Milan, Enrico; Mainoldi, Federica; Raimondi, Andrea; Fagioli, Claudio; Merlini, Arianna; Mariani, Elisabetta; Pasqualetto, Elena; Orfanelli, Ugo; Ponzoni, Maurilio; Sitia, Roberto; Casola, Stefano; Cenci, Simone.
Nat Immunol; 14(3): 298-305, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23354484
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.
Selo DaSilva