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Cocapture of cognate and bystander antigens can activate autoreactive B cells.

  • Sanderson NS Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland; nicholas.sanderson@unibas.ch tobias.derfuss@usb.ch.
  • Zimmermann M Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
  • Eilinger L Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
  • Gubser C Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
  • Schaeren-Wiemers N Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
  • Lindberg RL Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
  • Dougan SK Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
  • Ploegh HL Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
  • Kappos L Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
  • Derfuss T Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland; nicholas.sanderson@unibas.ch tobias.derfuss@usb.ch.
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  • 2017-01-07
Published in:
  • Proceedings of the National Academy of Sciences of the United States of America. - 2017
antigen capture
antigen presentation
autoantibodies
influenza
tolerance
Animals
Antigens, Viral
Autoantibodies
Autoantigens
Autoimmunity
B-Lymphocytes
Cell Line
Cell Membrane
HEK293 Cells
Hemagglutinin Glycoproteins, Influenza Virus
Humans
Mice
Mice, Inbred C57BL
Myelin-Oligodendrocyte Glycoprotein
Receptors, Antigen, B-Cell
T-Lymphocytes
English 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.
Language
  • English
Open access status
bronze
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Persistent URL
https://folia.unifr.ch/global/documents/73067
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