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Updated: Jun 9, 2025
Visualizing the Actin and Microtubule Cytoskeletons at the B-cell Immune Synapse Using Stimulated Emission Depletion STED Microscopy
Published on: April 9, 2018
B cell mechanosensing regulates ER remodeling at the immune synapse
Isidora Riobó1, María Isabel Yuseff1
1Immune Cell Biology Lab, Pontificia Universidad Católica de Chile, Facultad de Ciencias Biológicas, Santiago, Chile.
Insights
The endoplasmic reticulum (ER) moves to the immune synapse during B-cell activation, influenced by antigen presentation and surface stiffness. This ER remodeling impacts B-cell responses and early plasma cell development.
Area of Science:
- Immunology
- Cell Biology
- Biophysics
Background:
- B-cell receptor (BCR) engagement forms an immune synapse (IS) crucial for antigen processing.
- Calcium release from the endoplasmic reticulum (ER) upon BCR stimulation is vital for B-cell survival and differentiation.
- The role of ER spatial organization within the IS in modulating B-cell activation is not well understood.
Purpose of the Study:
- To investigate the spatial organization of the ER and its interaction with microtubules during BCR activation.
- To determine how mechanical cues from antigen-presenting surfaces influence ER remodeling at the IS.
- To understand how ER structure within the IS affects B-cell activation and function.
Main Methods:
- B-cells were cultured on surfaces with varying stiffness coated with BCR ligands.
- Cells were fixed and stained to visualize the ER and microtubule network.
- Imaging analysis quantified ER and microtubule distribution at the IS.
Main Results:
- Upon BCR activation, the ER redistributes towards the IS, independent of peripheral microtubules.
- ER accumulation occurs around the microtubule-organization center at the IS.
- Substrate stiffness significantly influences ER redistribution, with stiffer surfaces enhancing this process.
Conclusions:
- ER spatial reorganization at the IS is coupled to antigen recognition and can modulate B-cell responses.
- This study provides novel insights into the structural maturation of the ER in plasma cells, initiated during early B-cell activation.
- Mechanical cues from the cellular environment play a role in ER dynamics during immune synapse formation.
Introduction:
Engagement of the B-cell receptor with immobilized antigens triggers the formation of an immune synapse (IS), a complex cellular platform where B-cells recruit signaling molecules and reposition lysosomes to promote antigen uptake and processing. Calcium efflux from the endoplasmic reticulum (ER) released upon BCR stimulation is necessary to promote B-cell survival and differentiation. Whether the spatial organization of the ER within the B-cell synapse can tune IS function and B-cell activation remains unaddressed. Here, we characterized ER structure and interaction with the microtubule network during BCR activation and evaluated how mechanical cues arising from antigen presenting surfaces affect this process.
Methods:
B-cells were cultured on surfaces of varying stiffness coated with BCR ligands, fixed, and stained for the ER and microtubule network. Imaging analysis was used to assess the distribution of the ER and microtubules at the IS.
Results:
Upon BCR activation, the ER is redistributed towards the IS independently of peripheral microtubules and accumulates around the microtubule-organization center. Furthermore, this remodeling is also dependent on substrate stiffness, where greater stiffness triggers enhanced redistribution of the ER.
Discussion:
Our results highlight how spatial reorganization of the ER is coupled to the context of antigen recognition and could tune B-cell responses. Additionally, we provide novel evidence that the structural maturation of the ER in plasma cells is initiated during early activation of B-cells.
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