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Updated: Feb 24, 2026
Studying Organelle Dynamics in B Cells During Immune Synapse Formation
Published on: June 1, 2019
Caveolin-1-dependent nanoscale organization of the BCR regulates B cell tolerance
Susana Minguet1,2,3,4, Kathrin Kläsener1,2,5, Anna-Maria Schaffer1,3
1Department of Immunology, Institute for Biology III, Faculty of Biology, University of Freiburg, Freiburg, Germany.
Insights
Caveolin-1 regulates B cell receptor organization on the cell surface. This protein prevents autoimmunity by controlling B cell receptor signaling and development in mice.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Caveolin-1 (Cav1) is crucial for organizing the plasma membrane at the nanoscale.
- B cell antigen receptors (BCRs) are critical for adaptive immunity and self-tolerance.
Purpose of the Study:
- To investigate the role of Caveolin-1 in regulating B cell antigen receptor (BCR) nanoscale organization and its impact on B cell function and autoimmunity.
- To elucidate the molecular mechanisms by which Cav1 controls BCR distribution and signaling.
Main Methods:
- Analysis of B cell plasma membrane organization using nanoscale imaging techniques.
- Investigating the phosphorylation status of Cav1 and its interaction with Src family kinases.
- Studying B cell development, receptor editing, and repertoire formation in wild-type and Cav1-deficient mice.
- Assessing the development of autoimmunity in mouse models.
Main Results:
- Caveolin-1 controls the distribution of B cell antigen receptor (BCR) nanoclusters on the B cell surface.
- Antigen stimulation induces BCR nanocluster reorganization dependent on Cav1 phosphorylation by Src kinases, regulating BCR signaling.
- In immature Cav1-deficient B cells, aberrant BCR nanoscale organization impairs receptor editing, leading to poly- and auto-reactive B cells and autoimmunity in mice.
Conclusions:
- Caveolin-1 acts as a critical cell-intrinsic regulator of plasma membrane organization.
- Cav1's role in nanoscale BCR organization is essential for preventing B cell-induced autoimmunity.
- Targeting Cav1-mediated plasma membrane organization may offer therapeutic strategies for autoimmune diseases.
Abstract:
Caveolin-1 (Cav1) regulates the nanoscale organization and compartmentalization of the plasma membrane. Here we found that Cav1 controlled the distribution of nanoclusters of isotype-specific B cell antigen receptors (BCRs) on the surface of B cells. In mature B cells stimulated with antigen, the immunoglobulin M BCR (IgM-BCR) gained access to lipid domains enriched for GM1 glycolipids, by a process that was dependent on the phosphorylation of Cav1 by the Src family of kinases. Antigen-induced reorganization of nanoclusters of IgM-BCRs and IgD-BCRs regulated BCR signaling in vivo. In immature Cav1-deficient B cells, altered nanoscale organization of IgM-BCRs resulted in a failure of receptor editing and a skewed repertoire of B cells expressing immunoglobulin-micro heavy chains with hallmarks of poly- and auto-reactivity, which ultimately led to autoimmunity in mice. Thus, Cav1 emerges as a cell-intrinsic regulator that prevents B cell-induced autoimmunity by means of its role in plasma-membrane organization.
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