B cell receptor apoptotic signaling pathway

Definition

Target type: biologicalprocess

An extrinsic apoptotic signaling pathway initiated by the cross-linking of an antigen receptor on a B cell. [GOC:BHF, GOC:mtg_apoptosis, GOC:rl, PMID:15214043]

The B cell receptor (BCR) apoptotic signaling pathway is a crucial mechanism for eliminating self-reactive B cells and maintaining immune tolerance. It is triggered when BCRs engage with self-antigens, leading to a cascade of events that ultimately culminate in programmed cell death. Here's a detailed breakdown of the pathway:

1. **BCR Engagement and Signal Transduction:** When a B cell encounters a self-antigen, its BCR binds to the antigen, initiating a signaling cascade. This binding event leads to the activation of tyrosine kinases, including Lyn, Syk, and Bruton's tyrosine kinase (BTK). These kinases phosphorylate downstream signaling molecules, triggering a series of events that ultimately activate the apoptotic machinery.

2. **Activation of the PI3K/AKT Pathway:** One of the key downstream signaling pathways activated by BCR engagement is the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. PI3K is activated by the phosphorylation of phosphoinositide 3-kinase regulatory subunit 1 (PIK3R1), which leads to the production of phosphatidylinositol (3,4,5)-trisphosphate (PIP3). PIP3 then recruits AKT to the plasma membrane, where it is phosphorylated and activated by phosphoinositide-dependent kinase 1 (PDK1) and mTOR complex 2 (mTORC2).

3. **Activation of the MAPK Pathway:** The mitogen-activated protein kinase (MAPK) pathway is another important signaling pathway activated by BCR engagement. MAPKs are a family of serine/threonine kinases that are involved in various cellular processes, including proliferation, differentiation, and apoptosis. In the context of BCR signaling, MAPK activation can lead to both pro-survival and pro-apoptotic responses.

4. **Induction of Bim and Other Pro-Apoptotic Proteins:** Activation of the BCR signaling pathway leads to the induction of pro-apoptotic proteins such as Bim. Bim is a BH3-only protein that interacts with and activates the apoptotic machinery. The induction of Bim can be mediated by various mechanisms, including the activation of the PI3K/AKT pathway, the MAPK pathway, and the c-Jun N-terminal kinase (JNK) pathway.

5. **Activation of Caspases:** The final stages of BCR-mediated apoptosis involve the activation of caspases. Caspases are a family of cysteine proteases that play a central role in executing programmed cell death. Caspases are activated in a cascade, with upstream caspases (caspase-8 and caspase-9) activating downstream caspases (caspase-3, caspase-6, and caspase-7). These downstream caspases then cleave and degrade various cellular proteins, leading to the dismantling of the cell.

6. **Apoptosis and Cell Death:** The activation of caspases ultimately leads to the demise of the B cell. Apoptosis is a highly regulated process that results in the orderly dismantling of the cell, minimizing inflammation and damage to surrounding tissues. The apoptotic process ensures the elimination of self-reactive B cells, preventing the development of autoimmune diseases.

The BCR apoptotic signaling pathway is a highly complex process that involves numerous signaling molecules and pathways. It is essential for maintaining immune tolerance and preventing autoimmune disease. Dysregulation of this pathway can lead to the survival of self-reactive B cells and the development of autoimmune disorders.
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Proteins (1)

Compounds (2)