Building and operating an antibody factory: Redox control during B to plasma cell terminal differentiation

Silvia Masciarelli, Roberto Sitia

Research output: Contribution to journalArticle

Abstract

When small B lymphocytes bind their cognate antigens in the context of suitable signals, a dramatic differentiation program is activated that leads to the formation of plasma cells. These are short-lived specialized elements, each capable of secreting several thousands antibodies per second. The massive increase in Ig synthesis and transport entails a dramatic architectural and functional metamorphosis that involves the development of the endoplasmic reticulum (ER) and secretory organelles. Massive Ig secretion poses novel metabolic requirements, particularly for what concerns aminoacid import, ATP synthesis and redox homeostasis. Ig H and L chains enter the ER in the reduced state, to be rapidly oxidised mainly via protein driven relays based on the resident enzymes PDI and Ero1. How do plasma cells cope with the ensuing metabolic and redox stresses? In this essay, we discuss the physiological implications that increased Ig production could have in the control of plasma cell generation, function and lifespan, with emphasis on the potential role of ROS generation in mitochondria and ER.

Original languageEnglish
Pages (from-to)578-588
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1783
Issue number4
DOIs
Publication statusPublished - Apr 2008

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Keywords

  • Antibody secretion
  • Apoptosis
  • Differentiation
  • Oxidative folding
  • Oxidative stress
  • Plasma cells

ASJC Scopus subject areas

  • Biophysics
  • Cell Biology
  • Molecular Biology

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