Summary Thymic antigen-presenting cells (APCs) such as dendritic cells and medullary thymic epithelial cells (mTECs) use distinct strategies of self-antigen expression and presentation to mediate central tolerance. The thymus also harbors B cells; whether they also display unique tolerogenic features and how they genealogically relate to peripheral B cells is unclear. Here, we found that Aire is expressed in thymic but not peripheral B cells. Aire expression in thymic B cells coincided with major histocompatibility class \II\ (MHCII) and \CD80\ upregulation and immunoglobulin class-switching. These features were recapitulated upon immigration of naive peripheral B cells into the thymus, whereby this intrathymic licensing required \CD40\ signaling in the context of cognate interactions with autoreactive CD4+ thymocytes. Moreover, a licensing-dependent neo-antigen selectively upregulated in immigrating B cells mediated negative selection through direct presentation. Thus, autoreactivity within the nascent T cell repertoire fuels a feed forward loop that endows thymic B cells with tolerogenic features.
Description
Thymic B Cells Are Licensed to Present Self Antigens for Central T Cell Tolerance Induction
%0 Journal Article
%1 Yamano20151048
%A Yamano, Tomoyoshi
%A Nedjic, Jelena
%A Hinterberger, Maria
%A Steinert, Madlen
%A Koser, Sandra
%A Pinto, Sheena
%A Gerdes, Norbert
%A Lutgens, Esther
%A Ishimaru, Naozumi
%A Busslinger, Meinrad
%A Brors, Benedikt
%A Kyewski, Bruno
%A Klein, Ludger
%D 2015
%J Immunity
%K ABI-DKFZ
%N 6
%P 1048 - 1061
%R http://dx.doi.org/10.1016/j.immuni.2015.05.013
%T Thymic B Cells Are Licensed to Present Self Antigens for Central T Cell Tolerance Induction
%U http://www.sciencedirect.com/science/article/pii/S1074761315002113
%V 42
%X Summary Thymic antigen-presenting cells (APCs) such as dendritic cells and medullary thymic epithelial cells (mTECs) use distinct strategies of self-antigen expression and presentation to mediate central tolerance. The thymus also harbors B cells; whether they also display unique tolerogenic features and how they genealogically relate to peripheral B cells is unclear. Here, we found that Aire is expressed in thymic but not peripheral B cells. Aire expression in thymic B cells coincided with major histocompatibility class \II\ (MHCII) and \CD80\ upregulation and immunoglobulin class-switching. These features were recapitulated upon immigration of naive peripheral B cells into the thymus, whereby this intrathymic licensing required \CD40\ signaling in the context of cognate interactions with autoreactive CD4+ thymocytes. Moreover, a licensing-dependent neo-antigen selectively upregulated in immigrating B cells mediated negative selection through direct presentation. Thus, autoreactivity within the nascent T cell repertoire fuels a feed forward loop that endows thymic B cells with tolerogenic features.
@article{Yamano20151048,
abstract = {Summary Thymic antigen-presenting cells (APCs) such as dendritic cells and medullary thymic epithelial cells (mTECs) use distinct strategies of self-antigen expression and presentation to mediate central tolerance. The thymus also harbors B cells; whether they also display unique tolerogenic features and how they genealogically relate to peripheral B cells is unclear. Here, we found that Aire is expressed in thymic but not peripheral B cells. Aire expression in thymic B cells coincided with major histocompatibility class \{II\} (MHCII) and \{CD80\} upregulation and immunoglobulin class-switching. These features were recapitulated upon immigration of naive peripheral B cells into the thymus, whereby this intrathymic licensing required \{CD40\} signaling in the context of cognate interactions with autoreactive CD4+ thymocytes. Moreover, a licensing-dependent neo-antigen selectively upregulated in immigrating B cells mediated negative selection through direct presentation. Thus, autoreactivity within the nascent T cell repertoire fuels a feed forward loop that endows thymic B cells with tolerogenic features. },
added-at = {2015-06-30T10:17:45.000+0200},
author = {Yamano, Tomoyoshi and Nedjic, Jelena and Hinterberger, Maria and Steinert, Madlen and Koser, Sandra and Pinto, Sheena and Gerdes, Norbert and Lutgens, Esther and Ishimaru, Naozumi and Busslinger, Meinrad and Brors, Benedikt and Kyewski, Bruno and Klein, Ludger},
biburl = {https://www.bibsonomy.org/bibtex/2f09665ee4ec666ee149259053d4de4c6/juraeva},
description = {Thymic B Cells Are Licensed to Present Self Antigens for Central T Cell Tolerance Induction},
doi = {http://dx.doi.org/10.1016/j.immuni.2015.05.013},
interhash = {34449d69be5a228a7e3b703b531f6271},
intrahash = {f09665ee4ec666ee149259053d4de4c6},
issn = {1074-7613},
journal = {Immunity },
keywords = {ABI-DKFZ},
number = 6,
pages = {1048 - 1061},
timestamp = {2015-06-30T10:18:33.000+0200},
title = {Thymic B Cells Are Licensed to Present Self Antigens for Central T Cell Tolerance Induction },
url = {http://www.sciencedirect.com/science/article/pii/S1074761315002113},
volume = 42,
year = 2015
}