Related Experiment Video
Updated: Aug 20, 2025
A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins
Published on: March 22, 2012
Mechanism of CD79A and CD79B Support for IgM+ B Cell Fitness through B Cell Receptor Surface Expression
Kanutte Huse1,2, Baoyan Bai1,2,3, Vera I Hilden1,2
1Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Insights
CD79A and CD79B proteins are essential for surface IgM expression in human B cells, impacting B cell signaling and survival. Their absence causes immature protein accumulation and reduced cell fitness.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- The B cell receptor (BCR) complex, comprising surface immunoglobulin (Ig) and a CD79A/CD79B signaling unit, is crucial for B cell development and function.
- While the role of CD79A/CD79B heterodimers in BCR assembly and surface expression is known in mice, its investigation in human mature B cells is limited.
- Tonic signaling through the BCR provides essential Ag-independent survival signals for B cells.
Purpose of the Study:
- To investigate the role of CD79A and CD79B in surface IgM expression and BCR signaling in human mature B cells.
- To explore the impact of CD79A/CD79B deletion on B cell fitness and protein maturation.
- To elucidate the mechanism underlying surface IgM expression and its dependence on CD79A/CD79B heterodimerization.
Main Methods:
- CRISPR/Cas9-induced deletion of CD79A or CD79B in human B lymphoma cell lines.
- Analysis of surface IgM expression, B cell signaling, and cell fitness in knockout cell lines.
- Investigation of N-glycan maturation and protein localization using biochemical and cellular assays.
- Rescue experiments with wild-type and mutant CD79B to assess functional recovery.
Main Results:
- High surface IgM or IgG expression correlated with potentiated BCR signaling in human tonsillar B cells.
- Deletion of CD79A or CD79B abolished surface IgM expression in all tested B lymphoma cell lines.
- Loss of CD79A/CD79B led to impaired N-glycan maturation and ER retention of BCR components, reducing cell fitness.
- Rescue with wild-type CD79B restored surface IgM expression and mature glycosylation, unlike a heterodimerization-disrupting mutant.
Conclusions:
- CD79A and CD79B are indispensable for surface IgM expression in human B cells.
- The level of IgM expression influences BCR signaling and B cell fitness.
- Proper CD79A/CD79B heterodimerization is critical for BCR complex maturation and surface transport.
Abstract:
The BCR consists of surface-bound Ig and a heterodimeric signaling unit comprised of CD79A and CD79B. Upon cognate Ag recognition, the receptor initiates important signals for B cell development and function. The receptor also conveys Ag-independent survival signals termed tonic signaling. Although the requirement of a CD79A/CD79B heterodimer for BCR complex assembly and surface expression is well established based on mice models, few studies have investigated this in human mature B cells. In this study, we found that human tonsillar B cells with high surface expression of IgM or IgG had potentiated BCR signaling compared with BCRlow cells, and high IgM expression in germinal center B cells was associated with reduced apoptosis. We explored the mechanism for IgM surface expression by CRISPR/Cas9-induced deletion of CD79A or CD79B in four B lymphoma cell lines. Deletion of either CD79 protein caused loss of surface IgM in all cell lines and reduced fitness in three. From two cell lines, we generated stable CD79A or CD79B knockout clones and demonstrated that loss of CD79A or CD79B caused a block in N-glycan maturation and accumulation of immature proteins, compatible with retention of BCR components in the endoplasmic reticulum. Rescue experiments with CD79B wild-type restored surface expression of CD79A and IgM with mature glycosylation, whereas a naturally occurring CD79B G137S mutant disrupting CD79A/CD79B heterodimerization did not. Our study highlights that CD79A and CD79B are required for surface IgM expression in human B cells and illuminates the importance of the IgM expression level for signaling and fitness.
Related Concept Videos
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...
01:28Diversity of Antigen Receptors
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...
01:31Immunoglobulin-like Cell Adhesion Molecules
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
01:26Antigens Involved in Adaptive Immunity
Complete Antigens
Complete antigens possess both immunogenicity and...
01:31Antigen Processing Pathways
MHC Class I: Presenting Endogenous...