Plasma cells require autophagy for sustainable immunoglobulin production

N Pengo, M Scolari, L Oliva, E Milan, F Mainoldi… - Nature …, 2013 - nature.com
N Pengo, M Scolari, L Oliva, E Milan, F Mainoldi, A Raimondi, C Fagioli, A Merlini, E Mariani…
Nature immunology, 2013nature.com
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 …
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.
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