Related Experiment Video

Updated: Aug 10, 2026

Murine Model of CD40-activation of B cells
12:24

Murine Model of CD40-activation of B cells

Published on: March 6, 2010

CD40-mediated activation of Ig-Cgamma1- and Ig-cepsilon germ-line promoters involves multiple TRAF family proteins

E Leo1, J M Zapata, J C Reed

  • 1The Burnham Institute, La Jolla, CA 92037, USA.

European Journal of Immunology
|December 22, 1999
PubMed

Insights

CD40 signaling in B cells requires multiple TNF receptor-associated factors (TRAFs) for immunoglobulin class switching. Blocking TRAF2, TRAF3, TRAF5, or TRAF6 function disrupts this essential immune process.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • CD40 is crucial for B cell immunoglobulin (Ig) class switching.
  • The precise molecular mechanisms underlying CD40's role in this process are not fully understood.

Purpose of the Study:

  • To elucidate the specific roles of TNF receptor-associated factor (TRAF) family proteins in CD40-mediated signaling.
  • To investigate how TRAF interactions with CD40 influence germ-line immunoglobulin heavy chain (C(H)) promoter transcription.

Main Methods:

  • Utilized CD40 mutants defective in binding specific TRAF proteins.
  • Employed trans-dominant inhibitory forms of TRAF proteins.
  • Assessed transcriptional induction of germ-line Ig-Cgamma1 and Ig-Cepsilon promoters.
  • Investigated NF-kappaB-dependent mechanisms.

Main Results:

  • Mutations preventing TRAF2, TRAF3, TRAF5, or TRAF6 binding significantly reduced CD40-induced germ-line promoter transcription.
  • Inhibitory TRAF forms suppressed promoter induction.
  • TRAF2 and TRAF6 overexpression induced C(H) promoters via NF-kappaB.
  • TRAF3 and TRAF5 showed indirect roles.

Conclusions:

  • Multiple TRAF proteins play distinct, non-redundant roles in CD40 signal transduction.
  • These TRAFs are essential for germ-line C(H) promoter transcription, a prerequisite for Ig class switching.
  • Targeting these TRAF functions could offer therapeutic strategies to prevent B cell class switching.

More Related Videos

Characterization of Thymus-dependent and Thymus-independent Immunoglobulin Isotype Responses in Mice Using Enzyme-linked Immunosorbent Assay06:15

Characterization of Thymus-dependent and Thymus-independent Immunoglobulin Isotype Responses in Mice Using Enzyme-linked Immunosorbent Assay

Published on: September 7, 2018

Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice07:07

Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice

Published on: June 27, 2020

Related Concept Videos

Transcytosis of IgG01:15

Transcytosis of IgG

Transcytosis is the process in which molecules are internalized by endocytosis, transported across the cell, and released through exocytosis from the opposite end of the cell. Molecules such as insulin, immunoglobulins, and certain nutrients are transferred through the recycling endosomes by recycling and transcytosis.
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...