Protein kinase Cδ is essential for the IgG response against T-cell-independent type 2 antigens and commensal bacteria

Antigens (Ags) with multivalent and repetitive structure elicit IgG production in a T-cell-independent manner. However, the mechanisms by which such T-cell-independent type-2 (TI-2) Ags induce IgG responses remain obscure. Here, we report that B-cell receptor (BCR) engagement with a TI-2 Ag but not...

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Auteurs principaux:	Saori Fukao, Kei Haniuda, Hiromasa Tamaki, Daisuke Kitamura
Format:	article
Langue:	EN
Publié:	eLife Sciences Publications Ltd 2021
Sujets:	immune response B cells TI-2 class switching Medicine R Science Q Biology (General) QH301-705.5
Accès en ligne:	https://doaj.org/article/bacd8a89bd7e462fa3afbc6bbd3be148
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spelling	oai:doaj.org-article:bacd8a89bd7e462fa3afbc6bbd3be1482021-11-23T12:55:57ZProtein kinase Cδ is essential for the IgG response against T-cell-independent type 2 antigens and commensal bacteria10.7554/eLife.721162050-084Xe72116https://doaj.org/article/bacd8a89bd7e462fa3afbc6bbd3be1482021-10-01T00:00:00Zhttps://elifesciences.org/articles/72116https://doaj.org/toc/2050-084XAntigens (Ags) with multivalent and repetitive structure elicit IgG production in a T-cell-independent manner. However, the mechanisms by which such T-cell-independent type-2 (TI-2) Ags induce IgG responses remain obscure. Here, we report that B-cell receptor (BCR) engagement with a TI-2 Ag but not with a T-cell-dependent (TD) Ag was able to induce the transcription of Aicda encoding activation-induced cytidine deaminase (AID) and efficient class switching to IgG3 upon costimulation with IL-1 or IFN-α in mouse B cells. TI-2 Ags strongly induced the phosphorylation of protein kinase C (PKC)δ and PKCδ mediated the Aicda transcription through the induction of BATF, the key transcriptional regulator of Aicda. In PKCδ-deficient mice, production of IgG was intact against TD Ag but abrogated against typical TI-2 Ags as well as commensal bacteria, and experimental disruption of the gut epithelial barrier resulted in fatal bacteremia. Thus, our results have revealed novel molecular requirements for class switching in the TI-2 response and highlighted its importance in homeostatic commensal-specific IgG production.Saori FukaoKei HaniudaHiromasa TamakiDaisuke KitamuraeLife Sciences Publications Ltdarticleimmune responseB cellsTI-2class switchingMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	immune response B cells TI-2 class switching Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	immune response B cells TI-2 class switching Medicine R Science Q Biology (General) QH301-705.5 Saori Fukao Kei Haniuda Hiromasa Tamaki Daisuke Kitamura Protein kinase Cδ is essential for the IgG response against T-cell-independent type 2 antigens and commensal bacteria
description	Antigens (Ags) with multivalent and repetitive structure elicit IgG production in a T-cell-independent manner. However, the mechanisms by which such T-cell-independent type-2 (TI-2) Ags induce IgG responses remain obscure. Here, we report that B-cell receptor (BCR) engagement with a TI-2 Ag but not with a T-cell-dependent (TD) Ag was able to induce the transcription of Aicda encoding activation-induced cytidine deaminase (AID) and efficient class switching to IgG3 upon costimulation with IL-1 or IFN-α in mouse B cells. TI-2 Ags strongly induced the phosphorylation of protein kinase C (PKC)δ and PKCδ mediated the Aicda transcription through the induction of BATF, the key transcriptional regulator of Aicda. In PKCδ-deficient mice, production of IgG was intact against TD Ag but abrogated against typical TI-2 Ags as well as commensal bacteria, and experimental disruption of the gut epithelial barrier resulted in fatal bacteremia. Thus, our results have revealed novel molecular requirements for class switching in the TI-2 response and highlighted its importance in homeostatic commensal-specific IgG production.
format	article
author	Saori Fukao Kei Haniuda Hiromasa Tamaki Daisuke Kitamura
author_facet	Saori Fukao Kei Haniuda Hiromasa Tamaki Daisuke Kitamura
author_sort	Saori Fukao
title	Protein kinase Cδ is essential for the IgG response against T-cell-independent type 2 antigens and commensal bacteria
title_short	Protein kinase Cδ is essential for the IgG response against T-cell-independent type 2 antigens and commensal bacteria
title_full	Protein kinase Cδ is essential for the IgG response against T-cell-independent type 2 antigens and commensal bacteria
title_fullStr	Protein kinase Cδ is essential for the IgG response against T-cell-independent type 2 antigens and commensal bacteria
title_full_unstemmed	Protein kinase Cδ is essential for the IgG response against T-cell-independent type 2 antigens and commensal bacteria
title_sort	protein kinase cδ is essential for the igg response against t-cell-independent type 2 antigens and commensal bacteria
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/bacd8a89bd7e462fa3afbc6bbd3be148
work_keys_str_mv	AT saorifukao proteinkinasecdisessentialfortheiggresponseagainsttcellindependenttype2antigensandcommensalbacteria AT keihaniuda proteinkinasecdisessentialfortheiggresponseagainsttcellindependenttype2antigensandcommensalbacteria AT hiromasatamaki proteinkinasecdisessentialfortheiggresponseagainsttcellindependenttype2antigensandcommensalbacteria AT daisukekitamura proteinkinasecdisessentialfortheiggresponseagainsttcellindependenttype2antigensandcommensalbacteria
_version_	1718416724543406080

Protein kinase Cδ is essential for the IgG response against T-cell-independent type 2 antigens and commensal bacteria

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