B Cells Adapt Their Nuclear Morphology to Organize the Immune Synapse and Facilitate Antigen Extraction.

Romina Ulloa,Jorge Jara-Wilde,Jheimmy Diaz-Muñoz,Christopher Rivas,Fernanda Cabrera-Reyes,Clara Quiroga,María-Isabel Yuseff,Oreste Corrales,Steffen Härtel,Jonathan Lagos,Juan José Saez

doi:10.3389/fimmu.2021.801164

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.

Highlights

Efficient uptake and processing of foreign antigens by B cells is critical for their complete activation [1, 2]
We found that the antigen-coated bead became accommodated within the main nuclear groove near the microtubule-organizing center (MTOC), suggesting that B cells adapt their nuclear position and morphology to create a space to bring the MTOC closer to the synaptic interface
To confirm that this process was associated to B cell receptor (BCR) engagement, we examined the effect of Wheat germ agglutinin (WGA)-coated beads, an irrelevant ligand that interacts with cell surface glycans

Summary

Introduction

Efficient uptake and processing of foreign antigens by B cells is critical for their complete activation [1, 2]. B Cells Change Nuclear Morphology antigens at the center of the immune synapse [8,9,10,11]. B cells re-position the MTOC to the center of the synaptic membrane, which acts as a landmark to guide the polarized recruitment of lysosomes, which upon secretion can facilitate antigen extraction [12,13,14]. The tethering factor Exo, a subunit of the exocyst complex, was shown to be involved in lysosome docking at the synaptic membrane in B cells. Exo is associated to the MTOC in resting B cells and becomes repositioned to the synaptic membrane upon activation, helping to promote lysosome tethering and fusion [15]

Methods

Results

Conclusion