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In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
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The BiP cochaperone ERdj4 is required for B cell development and function.

Jill M Fritz1, Timothy E Weaver1

  • 1Perinatal Institute, Section of Neonatology, Perinatal and Pulmonary Biology Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.

Plos One
|September 16, 2014
PubMed
Summary
This summary is machine-generated.

The unfolded protein response chaperone ERdj4 is crucial for B cell development and antibody production. ERdj4 deficiency impairs B cell precursor survival, leading to reduced mature B cells and defective antibody responses.

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • ERdj4 is a BiP cochaperone involved in endoplasmic reticulum protein quality control.
  • The unfolded protein response (UPR) regulates ERdj4 and is vital for B cell maturation and antibody production.

Purpose of the Study:

  • To investigate the role of ERdj4 in B cell homeostasis and antibody production using gene trap mice.
  • To determine if ERdj4 chaperone activity is essential for B cell development and function.

Main Methods:

  • Generation and analysis of ERdj4 gene trap mice.
  • Flow cytometry to assess hematopoietic cell populations.
  • In vitro stimulation assays (LPS) and in vivo antigen challenge.

Main Results:

  • ERdj4 deficiency caused abnormal hematopoietic development, with reduced B lymphoid cells.
  • B cell precursors showed decreased survival, impacting B lymphopoiesis and mature B cell numbers.
  • Paradoxically, ERdj4-deficient B cells showed enhanced proliferation and isotype switching in vitro.
  • Mice failed to mount T cell-dependent antibody responses despite normal T cell-independent responses.

Conclusions:

  • ERdj4 chaperone activity is essential for the survival of B cell progenitors.
  • ERdj4 plays a critical role in maintaining B cell homeostasis and ensuring proper antibody production.