Bach2 repression of CD36 regulates lipid-metabolism-linked effector functions in follicular B cells
Eunkyeong Jang,
ChangYeon Kim,
Jeonghyun Noh,
Hansol Yi,
Sungsin Jo,
Jin-Sil Park,
Woochang Hwang,
Ji-Young Cha,
Mi-La Cho,
Tae-Hwan Kim,
Jeehee Youn
Affiliations
Eunkyeong Jang
Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, College of Medicine, Hanyang University, Seoul 04763, Korea; Corresponding author
ChangYeon Kim
Department of Biomedical Science, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, Korea
Jeonghyun Noh
Department of Biomedical Science, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, Korea
Hansol Yi
Department of Biomedical Science, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, Korea
Sungsin Jo
Hanyang University Institute for Rheumatology Research (HYIRR), Hanyang University, Seoul 04763, Korea
Jin-Sil Park
Rheumatism Research Center, Catholic Institutes of Medical Science, The Catholic University of Korea, Seoul 06591, Korea
Woochang Hwang
Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul 04763, Korea; Department of Pre-Medicine, College of Medicine, Hanyang University, Seoul 04763, Korea
Ji-Young Cha
Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21936, Korea
Mi-La Cho
Rheumatism Research Center, Catholic Institutes of Medical Science, The Catholic University of Korea, Seoul 06591, Korea
Tae-Hwan Kim
Hanyang University Institute for Rheumatology Research (HYIRR), Hanyang University, Seoul 04763, Korea
Jeehee Youn
Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, College of Medicine, Hanyang University, Seoul 04763, Korea; Department of Biomedical Science, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, Korea; Corresponding author
Summary: The transcription repressor Bach2 plays a crucial role in shaping humoral immunity, but its cell-autonomous function remains elusive. Here, we reveal the mechanism by which Bach2 regulates effector cell maturation in peripheral B cells. In response to Toll-like receptor (TLR) agonists, Bach2 deficiency promotes the differentiation of follicular, but not marginal zone, B cells into effector cells, producing interleukin (IL)-6 and antibodies. This phenomenon is associated with changes in lipid metabolism, such as increases in CD36 expression, lipid influx, and fatty acid oxidation. Consistent with this, Bach2-deficient B cells exhibit elevated levels of mitochondrial oxidative stress, lipid peroxidation, and p38 activation. Mechanistically, Bach2 acts as a repressor of Cd36, and inhibition of CD36 or fatty acid oxidation reduces the differentiation of naive B cells into IL-6- and antibody-secreting cells. These results indicate Bach2 as a key metabolic checkpoint regulator crucial for maintaining a functionally quiescent state of follicular B cells.
