Differential cell-intrinsic regulations of germinal center B and T cells by miR-146a and miR-146b PMID: 30013024

ADC Targets in Oncology

2026-04-10

Differential cell-intrinsic regulations of germinal center B and T cells by miR-146a and miR-146b

Nat Commun. 2018 Jul 16;9(1):2757. doi: 10.1038/s41467-018-05196-3.

Sunglim Cho ¹ , Hyang-Mi Lee ¹ , I-Shing Yu ² , Youn Soo Choi ³ ⁴ , Hsi-Yuan Huang ⁵ , Somaye Sadat Hashemifar ⁶ , Ling-Li Lin ¹ , Mei-Chi Chen ¹ , Nikita D Afanasiev ¹ , Aly Azeem Khan ⁶ , Shu-Wha Lin ⁷ ⁸ , Alexander Y Rudensky ⁹ , Shane Crotty ³ ¹⁰ , Li-Fan Lu ¹¹ ¹² ¹³

Affiliations

1. Division of Biological Sciences, University of California, La Jolla, San Diego, CA, 92093, USA.
2. Laboratory Animal Center, College of Medicine, National Taiwan University, Taipei, 100, Taiwan.
3. Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
4. Department of Medicine, College of Medicine, Seoul National University, Seoul, 03080, Korea.
5. Department of Laboratory Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan.
6. Toyota Technological Institute, Chicago, IL, 60637, USA.
7. Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan.
8. Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan.
9. Howard Hughes Medical Institute and Immunology Program, Ludwig Center at Memorial Sloan-Kettering Cancer Center, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
10. Division of Infectious Diseases, Department of Medicine, University of California, La Jolla, San Diego, CA, 92037, USA.
11. Division of Biological Sciences, University of California, La Jolla, San Diego, CA, 92093, USA. [email protected].
12. Moores Cancer Center, University of California, La Jolla, San Diego, CA, 92093, USA. [email protected].
13. Center for Microbiome Innovation, University of California, La Jolla, San Diego, CA, 92093, USA. [email protected].

Abstract

Reciprocal interactions between B and follicular T helper (Tfh) cells orchestrate the germinal center (GC) reaction, a hallmark of humoral immunity. Abnormal GC responses could lead to the production of pathogenic autoantibodies and the development of autoimmunity. Here we show that miR-146a controls GC responses by targeting multiple CD40 signaling pathway components in B cells; by contrast, loss of miR-146a in T cells does not alter humoral responses. However, specific deletion of both miR-146a and its paralog, miR-146b, in T cells increases Tfh cell numbers and enhanced GC reactions. Thus, our data reveal differential cell-intrinsic regulations of GC B and Tfh cells by miR-146a and miR-146b. Together, members of the miR-146 family serve as crucial molecular brakes to coordinately control GC reactions to generate protective humoral responses without eliciting unwanted autoimmunity.