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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
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...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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 activation may...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.

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Updated: May 10, 2026

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
10:26

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Published on: January 20, 2019

Notch-regulated periphery B cell differentiation involves suppression of E protein function.

Ping Zhang1, Ying Zhao, Xiao-Hong Sun

  • 1Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|June 12, 2013
PubMed
Summary
This summary is machine-generated.

Notch signaling opposes E protein activity to promote marginal zone B cell development over follicular B cells during B cell maturation. This study reveals key molecular mechanisms regulating peripheral B cell differentiation.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • The Notch signaling pathway is crucial for B cell maturation.
  • Its role in directing B cell fate towards marginal zone (MZ) or follicular (FO) subtypes is known, but underlying mechanisms remain unclear.

Purpose of the Study:

  • To investigate the molecular mechanisms by which Notch signaling regulates the balance between MZ and FO B cell generation.
  • To test the hypothesis that Notch signaling favors MZ B cells by downregulating E protein activity.

Main Methods:

  • Assessed expression of Id2 and ankyrin-repeat SOCS box-containing protein 2 in MZ B cells and in response to Notch signaling.
  • Analyzed splenic B cell phenotypes in mice with altered Notch1 and E protein activity.
  • Examined Bcl-6 expression and transitional B cell differentiation.

Main Results:

  • Notch signaling elevated Id2 and ankyrin-repeat SOCS box-containing protein 2, which inhibit and degrade E proteins, respectively.
  • Increased E protein activity promoted FO B cells and suppressed MZ B cells.
  • Conversely, elevated Notch1 favored MZ B cells and inhibited FO B cells, with effects reversed by gain-of-function E proteins.
  • Notch signaling reduced Bcl-6 in FO B cells, while E proteins restored it. E proteins promoted, and Notch hindered, transitional B cell differentiation.

Conclusions:

  • Notch signaling regulates peripheral B cell differentiation by antagonizing E protein function.
  • This antagonism is a key mechanism controlling the balance between MZ and FO B cell populations.