Autophagy, a new determinant of plasma cell differentiation and antibody responses

• Published in: Molecular immunology Vol. 62; no. 2; pp. 289 - 295
• Main Author: Cenci, Simone
• Format: Journal Article
• Language: English
• Published: England 01.12.2014
• Subjects: adaptive immunity; Animals; antibodies; Antibody Formation - immunology; autophagy; Autophagy - immunology; bone marrow; cell differentiation; Cell Differentiation - immunology; endoplasmic reticulum; energy; Humans; immunoglobulins; plasma cells; Plasma Cells - immunology; repressor proteins; viability; Ubiquitin; Immunological memory; Proteostasis; Antibody; Blimp-1; Multiple myeloma; Plasma cell; Reticulophagy; Autophagy; ER-phagy; Unfolded protein response; B cell; Endoplasmic reticulum; XBP-1; Atg5
• ISSN: 0161-5890; 1872-9142; 1872-9142
• DOI: 10.1016/j.molimm.2014.02.008

Plasma cells, the terminal effectors of the B lymphoid lineage, are responsible for the humoral arm of adaptive immunity. Their differentiation from B cells entails a profound cellular reshaping inherently associated with stress. Autophagy is a conserved adaptive cellular strategy recently implicated in differentiation and immunity. We identified a novel autophagic function in plasma cells. Autophagy restricts the expression of the transcriptional repressor Blimp-1 and immunoglobulins through a selective negative control on the endoplasmic reticulum and its stress signaling response, thereby optimizing energy and viability. As a result, autophagy in vivo sustains antibody responses, and is an essential intrinsic determinant of the bone marrow long-lived plasma cell niche. Here, I discuss several immune and biomedical implications, and experimental issues to be addressed in the near future.