CTLA-4 expression by B-1a B cells is essential for immune tolerance
In: Nature Communications Nature Communications, Jg. 12 (2021), Heft 1, S. 1-17
Online
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Zugriff:
CTLA-4 is an important regulator of T-cell function. Here, we report that expression of this immune-regulator in mouse B-1a cells has a critical function in maintaining self-tolerance by regulating these early-developing B cells that express a repertoire enriched for auto-reactivity. Selective deletion of CTLA-4 from B cells results in mice that spontaneously develop autoantibodies, T follicular helper (Tfh) cells and germinal centers (GCs) in the spleen, and autoimmune pathology later in life. This impaired immune homeostasis results from B-1a cell dysfunction upon loss of CTLA-4. Therefore, CTLA-4-deficient B-1a cells up-regulate epigenetic and transcriptional activation programs and show increased self-replenishment. These activated cells further internalize surface IgM, differentiate into antigen-presenting cells and, when reconstituted in normal IgH-allotype congenic recipient mice, induce GCs and Tfh cells expressing a highly selected repertoire. These findings show that CTLA-4 regulation of B-1a cells is a crucial immune-regulatory mechanism.
CTLA-4 is an important co-inhibitory receptor for T cells. Here, the authors show that CTLA-4 also has a function on B-1a cells, as conditional deletion results in activation of these cells and knockout mice develop an autoimmune profile.
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CTLA-4 expression by B-1a B cells is essential for immune tolerance
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Autor/in / Beteiligte Person: | Vilches-Moure, Jose G. ; Byrne-Steele, Miranda ; Min, Qing ; Wang, Ji-Yang ; Ma, Zhihai ; Qin, Guang ; Toonstra, Christian ; Wang, Chunlin ; Yang, Yang ; Li, Xiao ; Hong, Rongjian ; Snyder, Michael ; Wing, James B. ; Cheng, Yong ; Han, Jian ; Herzenberg, Leonore A. ; Wang, Lai-Xi ; Zhou, Gao ; Sakaguchi, Shimon ; Wang, Denong ; Youngyunpipatkul, Justin ; Yang, Qunying |
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Zeitschrift: | Nature Communications Nature Communications, Jg. 12 (2021), Heft 1, S. 1-17 |
Veröffentlichung: | 2020 |
Medientyp: | unknown |
ISSN: | 2041-1723 (print) |
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