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Cocapture of cognate and bystander antigens can activate autoreactive B cells

Authors :
Massachusetts Institute of Technology. Department of Biology
Ploegh, Hidde
Sanderson, Nicholas S. R.
Zimmermann, Maria
Eilinger, Luca
Gubser, Céline
Schaeren-Wiemers, Nicole
Lindberg, Raija L. P.
Dougan, Stephanie K.
Kappos, Ludwig
Derfuss, Tobias
Massachusetts Institute of Technology. Department of Biology
Ploegh, Hidde
Sanderson, Nicholas S. R.
Zimmermann, Maria
Eilinger, Luca
Gubser, Céline
Schaeren-Wiemers, Nicole
Lindberg, Raija L. P.
Dougan, Stephanie K.
Kappos, Ludwig
Derfuss, Tobias
Source :
National Academy of Sciences
Publication Year :
2018

Abstract

Autoantibodies against myelin oligodendrocyte glycoprotein (MOG) are associated with autoimmune central nervous system diseases like acute disseminated encephalomyelitis (ADEM). For ADEM, it is speculated that a preceding infection is the trigger of the autoimmune response, but the mechanism connecting the infection to the production of MOG antibodies remains a mystery. We reasoned that the ability of B cells to capture cognate antigen from cell membranes, along with small quantities of coexpressed “bystander” antigens, might enable B-cell escape from tolerance. We tested this hypothesis using influenza hemagglutinin as a model viral antigen and transgenic, MOG-specific B cells. Using flow cytometry and live and fixed cell microscopy, we show that MOG-specific B cells take up large amounts of MOG from cell membranes. Uptake of the antigen from the membrane leads to a strong activation of the capturing B cell. When influenza hemagglutinin is also present in the membrane of the target cell, it can be cocaptured with MOG by MOG-specific B cells via the B-cell receptor. Hemagglutinin and MOG are both presented to T cells, which in turn are activated and proliferate. As a consequence, MOG-specific B cells get help from hemagglutinin-specific T cells to produce anti-MOG antibodies. In vivo, the transfer of MOG-specific B cells into recipient mice after the cocapture of MOG and hemagglutinin leads to the production of class-switched anti-MOG antibodies, dependent on the presence of hemagglutinin-specific T cells. This mechanism offers a link between infection and autoimmunity. Keywords: tolerance; autoantibodies; antigen capture; antigen presentation; influenza

Details

Database :
OAIster
Journal :
National Academy of Sciences
Notes :
application/pdf
Publication Type :
Electronic Resource
Accession number :
edsoai.on1141879694
Document Type :
Electronic Resource