Crlz-1 controls germinal center reaction by relaying a Wnt signal to the Bcl-6 expression in centroblasts during humoral immune responses

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Title
Crlz-1 controls germinal center reaction by relaying a Wnt signal to the Bcl-6 expression in centroblasts during humoral immune responses
Author(s)
S Y Choi; J H Pi; Sung-Kyun Park; C J Kang
Bibliographic Citation
Journal of Immunology, vol. 203, no. 10, pp. 2630-2643
Publication Year
2019
Abstract
Crlz-1 was expressed along with Wnt3a in the rapidly proliferating centroblasts within the dark zone of germinal center (GC) during humoral immune responses. Significantly, Crlz-1 relayed a Wnt/β-catenin signal to the expression of Bcl-6, the master regulator of centroblasts, by mobilizing the cytoplasmic CBFβ into the nucleus to allow Runx/CBFβ heterodimerization and its subsequent binding to the Bcl-6 promoter. The knockdown of Crlz-1 or β-catenin, as well as inhibition of Wnt signaling in the centroblasts, led to the decreased expression of Bcl-6 and, thereby, the altered expression of its various target genes, resulting in their diminished proliferation. Consistently, the administration of Wnt inhibitors into the immunized mice impaired or abolished GC reaction, with concomitant decreases of Crlz-1 and Bcl-6 expression and, thus, centroblastic proliferation. Our observation that Wnt/β-catenin signaling via Crlz-1 regulates GC reaction would suggest developmental strategies for vaccine adjuvants and cancer therapeutics because both immune efficacy and accidental lymphoma depend on GC reaction. Our studies of Crlz-1 were performed using human cell lines, mice, and their primary cells.
ISSN
0022-1767
Publisher
Amer Assoc Immunologists
DOI
http://dx.doi.org/10.4049/jimmunol.1900326
Type
Article
Appears in Collections:
Division of Research on National Challenges > Infectious Disease Research Center > 1. Journal Articles
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