Related Experiment Video
Updated: Jun 29, 2025
09:49
Induction and Assessment of Class Switch Recombination in Purified Murine B Cells
Published on: August 13, 2010
19.1K
The immunoglobulin heavy chain super enhancer controls class switch recombination in developing B cells.
Audrey Dauba1, Emmanuelle Näser1, Dylan Andrieux1
1Institut de Pharmacologie Et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, Université Toulouse III - Paul Sabatier (UT3), CNRS UMR5089, 205 Route de Narbonne, BP 64182, 31077, Toulouse, France.
Scientific Reports
|March 29, 2024
Summary
The 3' regulatory region (3'RR) controls antibody class switching (CSR) in mature B cells. This study shows the 3'RR is also essential for CSR in developing B cells, particularly regulating switch transcription via the hs4 enhancer.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Class switch recombination (CSR) is vital for adaptive immunity, allowing B cells to change antibody class from IgM to IgG, IgE, or IgA.
- CSR is regulated by the 3' regulatory region (3'RR), a super-enhancer controlling immunoglobulin heavy constant genes (IgH) transcription in mature B cells.
- While CSR occurs in developing B cells, the regulatory mechanisms, especially the role of the 3'RR, remain poorly understood.
Purpose of the Study:
- To investigate the role of the 3' regulatory region (3'RR) in regulating switch transcription and class switch recombination (CSR) in developing B cells.
- To determine if 3'RR activity is essential for CSR in primary developing B cells.
- To elucidate the specific enhancers within the 3'RR that contribute to CSR regulation in developing B cells.
Main Methods:
- Utilized a mouse model genetically engineered to lack the 3' regulatory region (3'RR).
- Employed a specialized cell culture system designed to highly enrich for pro-B cells, a type of developing B cell.
- Analyzed the correlation between 3'RR enhancer transcription (specifically hs4) and CSR activity.
Main Results:
- The absence of the 3'RR significantly impaired switch transcription and CSR in developing B cells, confirming its necessity.
- The requirement for 3'RR activity in CSR demonstrated an isotype-specific variation.
- CSR regulation by the 3'RR in developing B cells correlated specifically with the transcriptional activity of the hs4 enhancer.
Conclusions:
- The 3' regulatory region (3'RR) is crucial for initiating switch transcription and enabling class switch recombination (CSR) in developing B cells, not just mature B cells.
- The hs4 enhancer within the 3'RR plays a key role in mediating CSR in developing B cells in an isotype-dependent manner.
- These findings highlight a conserved regulatory mechanism of the 3'RR across B cell development stages for adaptive immune response.
Related Concept Videos
01:28Diversity of Antigen Receptors
582
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
582
01:24B Cell Activation and Differentiation
1.7K
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...
1.7K
01:31Immunoglobulin-like Cell Adhesion Molecules
3.3K
Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
3.3K
01:25Antibody Structure and Classes
899
Antibodies, also known as immunoglobulins, are produced by B cells in response to foreign substances, such as bacteria and viruses. These proteins are critical for recognizing and neutralizing these substances, protecting the body from potential harm.
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
899
01:22T Cell Activation and Clonal Selection
721
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...
Naive T cells that have not yet encountered an antigen express two primary CD...
721
01:15Transcytosis of IgG
2.7K
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...
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...
2.7K