Editors' ChoiceImmunology

Keeping Antibody Production Going

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Science Signaling  26 Feb 2013:
Vol. 6, Issue 264, pp. ec53
DOI: 10.1126/scisignal.2004096

Plasma cells are long-lived antibody-producing cells that are differentiated from B cells that have been exposed to antigen. During plasma cell differentiation, the cells expand the size of their endoplasmic reticulum (ER) and enhance their protein folding ability to support the production of large amounts of antibodies. Such intense protein production stresses these cells. Noting that autophagy, an intracellular degradative process that helps cells to survive nutrient deprivation and dispose of defective proteins and organelles, is used to counterbalance cellular stress in other systems, Pengo et al. investigated a role for autophagy in plasma cells. Immunofluorescence analysis showed that plasma cells isolated from immunized mice had increased numbers of autophagosomes (autophagic vesicles) than did B cells from the same mice. Mass spectrometric comparison of plasma cells from wild-type mice with those from mice with a B cell–specific deletion of the gene encoding the essential autophagic factor Atg5 showed that antibodies and ER-resident proteins were enhanced in abundance in the absence of Atg5. Electron microscopy showed that Atg5-deficient plasma cells had ERs that were 40% larger than those of wild-type cells. In addition, the Atg5-deficient plasma cells had increased markers of the ER stress response. Metabolic studies showed that Atg5-deficient plasma cells activated with lipopolysaccharide had decreased amounts of cellular ATP compared with those of activated wild-type plasma cells. Activation also resulted in increased apoptosis in the Atg5-deficient cells. Together with data from experiments that showed that mice with a B cell–specific deficiency in Atg5 had impaired antibody responses and fewer long-lived plasma cells compared with wild-type mice, these findings suggest that autophagy limits ER expansion so that plasma cells survive and maintain antibody production, which is essential for long-term immunity.

N. Pengo, M. Scolari, L. Oliva, E. Milan, F. Mainoldi, A. Raimondi, C. Fagioli, A. Merlini, E. Mariani, E. Pasqualetto, U. Orfanelli, M. Ponzoni, R. Sitia, S. Casola, S. Cenci, Plasma cells require autophagy for sustainable immunoglobulin production. Nat. Immunol. 14, 298–305 (2013). [PubMed]

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