Related Experiment Video

Updated: Apr 26, 2026

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

13.9K

Adaptor protein DOK3 promotes plasma cell differentiation by regulating the expression of programmed cell death 1

Xijun Ou1, Shengli Xu2, Yan-Feng Li1

  • 1Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore 138668;

Proceedings of the National Academy of Sciences of the United States of America
|July 24, 2014
PubMed

Insights

Downstream-of-Kinase 3 (DOK3) regulates plasma cell differentiation by controlling calcium signaling and programmed cell death ligand expression. Its absence impairs antibody production, highlighting DOK3

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Signaling

Background:

  • Downstream-of-Kinase 3 (DOK3) negatively regulates B-cell receptor signaling.
  • DOK3 is not essential for early B-cell development but its role in plasma cell differentiation is unclear.

Purpose of the Study:

  • To investigate the role of DOK3 in plasma cell differentiation.
  • To elucidate the molecular mechanisms by which DOK3 influences plasma cell development.

Main Methods:

  • Analysis of Dok3(-/-) mice immunized with T-cell-dependent antigens.
  • Bone marrow reconstitution experiments.
  • Assessment of programmed cell death 1 (PD-1) ligand expression and calcium signaling pathways.

Main Results:

  • Dok3(-/-) mice exhibit increased T follicular-helper and germinal center B cells but reduced plasma cells.
  • The plasma cell defect in Dok3(-/-) B cells is intrinsic and linked to impaired PD-1 ligand expression.
  • Overexpression of PD-1 ligand 2 (PDL2) rescues the plasma cell differentiation defect.
  • Calcium signaling suppresses PD-1 ligand transcription; its abrogation increases PD-1 ligand expression.

Conclusions:

  • DOK3 is a critical regulator of plasma cell differentiation.
  • DOK3 promotes plasma cell development by attenuating calcium signaling, thereby up-regulating PD-1 ligand expression.
  • This pathway is essential for effective antibody production.

More Related Videos

Assessing the Development of Murine Plasmacytoid Dendritic Cells in Peyer's Patches Using Adoptive Transfer of Hematopoietic Progenitors13:34

Assessing the Development of Murine Plasmacytoid Dendritic Cells in Peyer's Patches Using Adoptive Transfer of Hematopoietic Progenitors

Published on: March 17, 2014

10.4K
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood06:07

Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood

Published on: February 5, 2020

5.3K

Related Concept Videos

B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
14.3K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.0K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.0K
Immunoglobulin-like Cell Adhesion Molecules01:31

Immunoglobulin-like Cell Adhesion Molecules

Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
3.3K