Related Experiment Video
Updated: Aug 19, 2025
10:26
In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
Published on: January 20, 2019
12.4K
A p38α-BLIMP1 signalling pathway is essential for plasma cell differentiation
Jianfeng Wu1,2, Kang Yang1, Shaowei Cai1
1State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China.
Nature Communications
|November 28, 2022
Summary
The p38-alpha kinase is crucial for plasma cell differentiation and antibody production by regulating BLIMP1 expression. This pathway is essential for both T cell-independent and T cell-dependent humoral immune responses.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Plasma cells (PCs) are vital antibody-secreting cells in humoral immunity.
- PC differentiation is regulated by the transcription factor BLIMP1.
- The role of p38 mitogen-activated protein kinase alpha (p38α) in B cell differentiation remains unclear.
Purpose of the Study:
- To investigate the specific role of p38α in B cell differentiation into plasma cells.
- To elucidate the molecular mechanisms by which p38α influences PC differentiation.
- To identify downstream targets of p38α in the context of humoral immune responses.
Main Methods:
- Generation of B cell-specific p38α knockout mice.
- Analysis of B cell development and humoral immune responses.
- Use of a Blimp1 reporter mouse model.
- CRISPR/Cas9 screening to identify downstream effectors.
Main Results:
- B cell-specific deletion of p38α severely impaired PC differentiation and antibody responses.
- B cell development and germinal center B cell responses were unaffected.
- p38α deficiency led to reduced BLIMP1 expression.
- p38α signaling upregulates BLIMP1, which is essential for both T cell-independent and T cell-dependent PC differentiation.
- TCF3, TCF4, and IRF4 were identified as downstream effectors of p38α controlling BLIMP1 transcription.
Conclusions:
- p38α plays a specialized and non-redundant role in PC differentiation, acting upstream of BLIMP1.
- The p38α-BLIMP1 signaling axis is critical for effective humoral immunity.
- This study reveals a key pathway regulating plasma cell development.
Related Concept Videos
01:24B Cell Activation and Differentiation
3.8K
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...
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...
3.8K
01:16TGF - β Signaling Pathway
7.6K
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...
7.6K
01:31The Intrinsic Apoptotic Pathway
6.7K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.7K
01:19Interactions Between Signaling Pathways
6.4K
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...
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...
6.4K
01:20The JAK-STAT Signaling Pathway
9.1K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
9.1K
02:26NF-κB-dependent Signaling Pathway
7.8K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.8K