Autophagy in plasma cell pathophysiology

Laura Oliva, Simone Cenci

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Plasma cells (PCs) are the effectors responsible for antibody (Ab)-mediated immunity. They differentiate from B lymphocytes through a complete remodeling of their original structure and function. Stress is a constitutive element of PC differentiation. Macroautophagy, conventionally referred to as autophagy, is a conserved lysosomal recycling strategy that integrates cellular metabolism and enables adaptation to stress. In metazoa, autophagy plays diverse roles in cell differentiation. Recently, a number of autophagic functions have been recognized in innate and adaptive immunity, including clearance of intracellular pathogens, inflammasome regulation, lymphocyte ontogenesis, and antigen presentation. We identified a previously unrecognized role played by autophagy in PC differentiation and activity. Following B cell activation, autophagy moderates the expression of the transcriptional repressor Blimp-1 and immunoglobulins through a selective negative control exerted on the size of the endoplasmic reticulum and its stress signaling response, including the essential PC transcription factor, XBP-1. This containment of PC differentiation and function, i.e., Ab production, is essential to optimize energy metabolism and viability. As a result, autophagy sustains Ab responses in vivo. Moreover, autophagy is an essential intrinsic determinant of long-lived PCs in their as yet poorly understood bone marrow niche. In this essay, we discuss these findings in the context of the established biological functions of autophagy, and their manifold implications for adaptive immunity and PC diseases, in primis multiple myeloma.

Original languageEnglish
Article numberArticle 103
JournalFrontiers in Immunology
Volume5
Issue numberMAR
DOIs
Publication statusPublished - 2014

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Autophagy
Plasma Cells
Cell Differentiation
Adaptive Immunity
Antibody Formation
B-Lymphocytes
Inflammasomes
Endoplasmic Reticulum Stress
Antigen Presentation
Recycling
Multiple Myeloma
Innate Immunity
Energy Metabolism
Immunoglobulins
Immunity
Transcription Factors
Bone Marrow
Lymphocytes
Antibodies

Keywords

  • Antibody
  • Autophagy
  • Endoplasmic reticulum
  • Multiple myeloma
  • Plasma cell
  • Proteostasis
  • Unfolded protein response
  • XBP-1

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Autophagy in plasma cell pathophysiology. / Oliva, Laura; Cenci, Simone.

In: Frontiers in Immunology, Vol. 5, No. MAR, Article 103, 2014.

Research output: Contribution to journalArticle

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