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Related Experiment Videos

Modulating secretion of antibodies.

A M Fra1, C Alberini, P Bet

  • 1Istituto Scientifico San Raffaele, Milano, Italy.

Annales De Biologie Clinique
|January 1, 1991
PubMed
Summary
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Cells control protein quality by retaining misfolded IgM. Reducing agents allow secretion of IgM assembly intermediates, revealing a novel quality control mechanism in B lymphocytes.

Area of Science:

  • Cellular Biology
  • Immunology
  • Protein Biochemistry

Background:

  • Cells possess sophisticated quality control mechanisms to ensure proper protein folding and assembly.
  • Plasma cells secrete polymeric IgM, retaining and degrading intracellular assembly intermediates.
  • B lymphocytes fail to polymerize and secrete IgM, expressing only the membrane-bound form due to assembly issues.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying the retention and degradation of IgM assembly intermediates.
  • To elucidate the role of disulphide interchange reactions in IgM quality control.
  • To understand how reducing conditions affect IgM transport and secretion.

Main Methods:

  • Analysis of IgM polymerization and secretion in B lymphocytes and plasma cells.

Related Experiment Videos

  • Investigation of disulphide interchange reactions involving IgM subunits and endoplasmic reticulum proteins.
  • Assessment of the impact of reducing agents on IgM transport through the secretory pathway.

    • Main Results:

    • Selective retention of IgM assembly intermediates is mediated by disulphide interchange reactions.
    • These reactions involve the C-terminal cysteine of secretory IgM subunits and unknown endoplasmic reticulum proteins.
    • Addition of reducing agents inhibits these reactions, promoting transport, glycosylation, and secretion of IgM intermediates.

    Conclusions:

    • IgM secretion is tightly regulated by a quality control system within the endoplasmic reticulum.
    • Disulphide interchange reactions are key to retaining incompletely assembled IgM.
    • Intervention with reducing agents can overcome this retention, enabling secretion of IgM assembly intermediates.