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B cell receptor ligation induces display of V-region peptides on MHC class II molecules to T cells

The B cell receptors (BCRs) for antigen express variable (V) regions that are enormously diverse, thus serving as markers on individual B cells. V region-derived idiotypic (Id) peptides can be displayed as pId:MHCII complexes on B cells for recognition by CD4(+) T cells. It is not known if naive B c...

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Autores principales: Huszthy, Peter Csaba, Gopalakrishnan, Ramakrishna Prabhu, Jacobsen, Johanne Tracey, Haabeth, Ole Audun Werner, Løset, Geir Åge, Braathen, Ranveig, Schenck, Karl, Tveita, Anders Aune, Munthe, Ludvig Andre, Bogen, Bjarne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926052/
https://www.ncbi.nlm.nih.gov/pubmed/31796587
http://dx.doi.org/10.1073/pnas.1902836116
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author Huszthy, Peter Csaba
Gopalakrishnan, Ramakrishna Prabhu
Jacobsen, Johanne Tracey
Haabeth, Ole Audun Werner
Løset, Geir Åge
Braathen, Ranveig
Schenck, Karl
Tveita, Anders Aune
Munthe, Ludvig Andre
Bogen, Bjarne
author_facet Huszthy, Peter Csaba
Gopalakrishnan, Ramakrishna Prabhu
Jacobsen, Johanne Tracey
Haabeth, Ole Audun Werner
Løset, Geir Åge
Braathen, Ranveig
Schenck, Karl
Tveita, Anders Aune
Munthe, Ludvig Andre
Bogen, Bjarne
author_sort Huszthy, Peter Csaba
collection PubMed
description The B cell receptors (BCRs) for antigen express variable (V) regions that are enormously diverse, thus serving as markers on individual B cells. V region-derived idiotypic (Id) peptides can be displayed as pId:MHCII complexes on B cells for recognition by CD4(+) T cells. It is not known if naive B cells spontaneously display pId:MHCII in vivo or if BCR ligation is required for expression, thereby enabling collaboration between Id(+) B cells and Id-specific T cells. Here, using a mouse model, we show that naive B cells do not express readily detectable levels of pId:MHCII. However, BCR ligation by Ag dramatically increases physical display of pId:MHCII, leading to activation of Id-specific CD4(+) T cells, extrafollicular T–B cell collaboration and some germinal center formation, and production of Id(+) IgG. Besides having implications for immune regulation, the results may explain how persistent activation of self-reactive B cells induces the development of autoimmune diseases and B cell lymphomas.
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spelling pubmed-69260522019-12-23 B cell receptor ligation induces display of V-region peptides on MHC class II molecules to T cells Huszthy, Peter Csaba Gopalakrishnan, Ramakrishna Prabhu Jacobsen, Johanne Tracey Haabeth, Ole Audun Werner Løset, Geir Åge Braathen, Ranveig Schenck, Karl Tveita, Anders Aune Munthe, Ludvig Andre Bogen, Bjarne Proc Natl Acad Sci U S A PNAS Plus The B cell receptors (BCRs) for antigen express variable (V) regions that are enormously diverse, thus serving as markers on individual B cells. V region-derived idiotypic (Id) peptides can be displayed as pId:MHCII complexes on B cells for recognition by CD4(+) T cells. It is not known if naive B cells spontaneously display pId:MHCII in vivo or if BCR ligation is required for expression, thereby enabling collaboration between Id(+) B cells and Id-specific T cells. Here, using a mouse model, we show that naive B cells do not express readily detectable levels of pId:MHCII. However, BCR ligation by Ag dramatically increases physical display of pId:MHCII, leading to activation of Id-specific CD4(+) T cells, extrafollicular T–B cell collaboration and some germinal center formation, and production of Id(+) IgG. Besides having implications for immune regulation, the results may explain how persistent activation of self-reactive B cells induces the development of autoimmune diseases and B cell lymphomas. National Academy of Sciences 2019-12-17 2019-12-03 /pmc/articles/PMC6926052/ /pubmed/31796587 http://dx.doi.org/10.1073/pnas.1902836116 Text en Copyright © 2019 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle PNAS Plus
Huszthy, Peter Csaba
Gopalakrishnan, Ramakrishna Prabhu
Jacobsen, Johanne Tracey
Haabeth, Ole Audun Werner
Løset, Geir Åge
Braathen, Ranveig
Schenck, Karl
Tveita, Anders Aune
Munthe, Ludvig Andre
Bogen, Bjarne
B cell receptor ligation induces display of V-region peptides on MHC class II molecules to T cells
title B cell receptor ligation induces display of V-region peptides on MHC class II molecules to T cells
title_full B cell receptor ligation induces display of V-region peptides on MHC class II molecules to T cells
title_fullStr B cell receptor ligation induces display of V-region peptides on MHC class II molecules to T cells
title_full_unstemmed B cell receptor ligation induces display of V-region peptides on MHC class II molecules to T cells
title_short B cell receptor ligation induces display of V-region peptides on MHC class II molecules to T cells
title_sort b cell receptor ligation induces display of v-region peptides on mhc class ii molecules to t cells
topic PNAS Plus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926052/
https://www.ncbi.nlm.nih.gov/pubmed/31796587
http://dx.doi.org/10.1073/pnas.1902836116
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