Related Experiment Video
Updated: Jun 26, 2026
Interview: Glycolipid Antigen Presentation by CD1d and the Therapeutic Potential of NKT cell Activation
Published on: January 1, 2008
Jun N-terminal kinase is essential for CD40-mediated IgE class switching in B cells
1Division of Immunology, Children's Hospital, KARP Building #10126, 1 Blackfan Circle, Boston, MA 02115, USA. Haifa.jubara@childrens.harvard.edu
Insights
C-Jun N-terminal kinase (JNK) activation is crucial for CD40-mediated immunoglobulin class-switch recombination (CSR) to IgE in B cells. This study demonstrates JNK’s essential role in the CSR process, highlighting its importance for activation-induced deaminase (AID) activity.
Area of Science:
- Immunology
- Molecular Biology
Background:
- CD40 ligation activates NF-kappaB, p38, and JNK, driving B cell immunoglobulin class-switch recombination (CSR).
- NF-kappaB and p38 are known to be important for CD40-mediated CSR.
- The specific role of JNK activation in CD40-mediated isotype switching remained undetermined.
Purpose of the Study:
- To elucidate the role of JNK activation in CD40-mediated isotype switching in B cells.
Main Methods:
- Splenic B cells were stimulated with anti-CD40 or soluble CD40 ligand, with or without the JNK inhibitor SP600125.
- Assessed IgE production, switch recombination (S(mu)-S(epsilon)), germline and mature epsilon and AID transcription, B cell proliferation, and surface marker expression.
Main Results:
- SP600125 significantly inhibited JNK phosphorylation but minimally affected p38 phosphorylation and NF-kappaB-dependent gene expression.
- IgE synthesis was reduced by approximately 88% with SP600125 treatment.
- SP600125 did not impact B cell proliferation or survival, nor CD23, CD54, CD86 upregulation.
- While C(epsilon) germline and AID transcription were unaffected, S(mu)-S(epsilon) recombination and mature epsilon transcript expression were severely reduced.
Conclusions:
- JNK activation is essential for CD40-mediated CSR to IgE in B cells.
- JNK appears to play a critical role in regulating activation-induced deaminase (AID) activity during IgE class switching.
Background:
CD40 ligation activates nuclear factor kappaB (NF-kappaB) and the mitogen-activated protein kinases p38 and C-Jun N-terminal kinase (JNK) and causes immunoglobulin class-switch recombination (CSR) in B cells. Both NF-kappaB and p38 are important for CD40-mediated CSR. The role of JNK activation in CD40-mediated isotype switching is unknown.
Objective:
We sought to determine the role of JNK activation in CD40-mediated isotype switching.
Methods:
Splenic B cells from BALB/c mice were stimulated with anti-CD40 mAb and IL-4 or with soluble CD40 ligand in the presence or absence of SP600125, an anthrapyrazolone inhibitor of JNK. The following events were examined: IgE production by means of ELISA; S(mu)-S(epsilon) deletional switch recombination by means of digestion circularization PCR; Cepsilon germline, mature epsilon, and activation-induced deaminase (AID) transcription by means of RT-PCR; and proliferation by tritiated thymidine incorporation and surface expression of CD23, CD54, and CD86 by means of FACS analysis.
Results:
SP600125 at 10 microM drastically inhibited JNK phosphorylation but had little effect on CD40-mediated p38 phosphorylation and expression of the NF-kappaB dependent genes c-Myc and bcl-xL. SP600125 inhibited IgE synthesis by approximately 88% but had no effect on B-cell proliferation and survival in response to anti-CD40 + IL-4 or on upregulation of CD23, CD54, and CD86 in response to CD40 ligation. Analysis of molecular events involved in IgE class switching revealed that SP600125 had no effect on the expression of C(epsilon) germline and AID transcripts. In contrast, SP600125 severely reduced S(mu)-S(epsilon) switch recombination and expression of mature epsilon transcripts.
Conclusion:
These results demonstrate that JNK activation is essential for CD40-mediated CSR to IgE and suggest that JNK is important for AID activity in B cells.
Related Concept Videos
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
02:26NF-kB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
01:25Immune Surveillance by NK Cells and Phagocytes
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
01:22T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
01:24B Cell Activation and Differentiation
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...