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Updated: Oct 2, 2025

Studying Organelle Dynamics in B Cells During Immune Synapse Formation
Published on: June 1, 2019
B Cells Adapt Their Nuclear Morphology to Organize the Immune Synapse and Facilitate Antigen Extraction
Romina Ulloa1, Oreste Corrales1, Fernanda Cabrera-Reyes1
1Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Insights
B cells adapt nuclear shape and position to form immune synapses for antigen extraction. Nuclear envelope proteins Nesprin-1 and Sun-1 are crucial for this process, ensuring proper B cell activation.
Area of Science:
- Immunology
- Cell Biology
- Biophysics
Background:
- B cells form immune synapses to extract antigens.
- Nuclear morphology's role in B cell immune synapse formation was previously unaddressed.
- Actin remodeling and microtubule-organizing center (MTOC) positioning are key to antigen extraction.
Purpose of the Study:
- To investigate the role of nuclear morphology and positioning in B cell immune synapse formation.
- To determine the involvement of nuclear envelope proteins Nesprin-1 and Sun-1 in B cell activation.
Main Methods:
- Studied B cell activation and immune synapse formation.
- Utilized gene silencing of nuclear envelope proteins Nesprin-1 and Sun-1.
- Analyzed actin organization, MTOC and lysosome positioning, and B cell receptor (BCR) internalization.
Main Results:
- Activated B cells re-orient and groove their nuclei towards the immune synapse.
- Silencing Nesprin-1 and Sun-1 impaired nuclear reorientation and actin organization.
- Nesprin-1 and Sun-1-silenced B cells showed defective Exo70 accumulation, lysosome positioning, and BCR internalization, hindering antigen extraction.
Conclusions:
- Nuclear morphology and positioning are critical for coordinating B cell activation.
- Nesprin-1 and Sun-1 play essential roles in regulating nuclear adaptation during immune synapse formation.
- Defects in nuclear positioning impair B cell antigen uptake and activation efficiency.
Abstract:
Upon interaction with immobilized antigens, B cells form an immune synapse where actin remodeling and re-positioning of the microtubule-organizing center (MTOC) together with lysosomes can facilitate antigen extraction. B cells have restricted cytoplasmic space, mainly occupied by a large nucleus, yet the role of nuclear morphology in the formation of the immune synapse has not been addressed. Here we show that upon activation, B cells re-orientate and adapt the size of their nuclear groove facing the immune synapse, where the MTOC sits, and lysosomes accumulate. Silencing the nuclear envelope proteins Nesprin-1 and Sun-1 impairs nuclear reorientation towards the synapse and leads to defects in actin organization. Consequently, B cells are unable to internalize the BCR after antigen activation. Nesprin-1 and Sun-1-silenced B cells also fail to accumulate the tethering factor Exo70 at the center of the synaptic membrane and display defective lysosome positioning, impairing efficient antigen extraction at the immune synapse. Thus, changes in nuclear morphology and positioning emerge as critical regulatory steps to coordinate B cell activation.
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