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.
Plasma cells require autophagy for sustainable immunoglobulin production / 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.. - In: NATURE IMMUNOLOGY. - ISSN 1529-2908. - 14:3(2013), pp. 298-305. [10.1038/ni.2524]