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

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, y...

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Bibliographic Details
Published in:Frontiers in immunology 2022-02, Vol.12, p.801164-801164
Main Authors: Ulloa, Romina, Corrales, Oreste, Cabrera-Reyes, Fernanda, Jara-Wilde, Jorge, Saez, Juan José, Rivas, Christopher, Lagos, Jonathan, Härtel, Steffen, Quiroga, Clara, Yuseff, María-Isabel, Diaz-Muñoz, Jheimmy
Format: Article
Language:English
Subjects:
actin cytoskeleton
Actins - metabolism
Antigens - metabolism
B cells
B-Lymphocytes
immune synapse
Immunology
Nesprin-1
nuclear morphology
Receptors, Antigen, B-Cell - metabolism
Sun-1
Synapses - metabolism
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Summary: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.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.801164