Impaired inducibility of immune regulatory capacity of peripheral B cells of patients with recurrent pregnancy loss

Fei Ma; Xiaoyang Feng; Shiyu Feng; Jin Liu; Jia Li; Lihua Mo; Lingzhi Xu; Yulei Liu; Jiaman Wu; Pingchang Yang; Yan Ning

doi:10.1007/s12026-024-09549-7

Impaired inducibility of immune regulatory capacity of peripheral B cells of patients with recurrent pregnancy loss

Immunol Res. 2024 Nov 4. doi: 10.1007/s12026-024-09549-7. Online ahead of print.

Authors

Fei Ma^{1

2}, Xiaoyang Feng³, Shiyu Feng³, Jin Liu³, Jia Li³, Lihua Mo^{4

5}, Lingzhi Xu⁶, Yulei Liu⁷, Jiaman Wu⁷, Pingchang Yang⁸, Yan Ning⁹

Affiliations

¹ Department of Chinese Traditional Medicine, Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen, China. [email protected].
² School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China. [email protected].
³ School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
⁴ Department of General Practice Medicine, Third Affiliated Hospital of Shenzhen University, Shenzhen, China.
⁵ Institute of Allergy & Immunology of Shenzhen University, State Key Laboratory of Respiratory Diseases Allergy Division, Shenzhen University, Room A7-509 at Lihu Campus of Shenzhen University, 1066 Xueyuan Blvd, Shenzhen, 518055, China.
⁶ Department of Immunology, School of Basic Medical Sciences, Weifang Medical University, Weifang, China.
⁷ Department of Chinese Traditional Medicine, Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen, China.
⁸ Institute of Allergy & Immunology of Shenzhen University, State Key Laboratory of Respiratory Diseases Allergy Division, Shenzhen University, Room A7-509 at Lihu Campus of Shenzhen University, 1066 Xueyuan Blvd, Shenzhen, 518055, China. [email protected].
⁹ Department of Chinese Traditional Medicine, Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen, China. [email protected].

PMID: 39495420
DOI: 10.1007/s12026-024-09549-7

Abstract

The pathogenesis of recurrent pregnancy loss (RPL) is unclear. RPL may have an association with disruption of immune tolerance. The aim of this study is to characterize the inducibility of immune regulatory ability in peripheral naïve B cells of patients with RPL. In this study, blood samples were taken from patients with RPL. B220⁺ B cells were isolated by flow cytometry cell sorting. The gene profile of B cells was analyzed using RNA sequencing (RNAseq). The results showed that peripheral B220⁺ B cells of RPL patients had lower expression of IL10 and exacerbated ER stress. The induction of IL10 expression in peripheral B220⁺ B cells of RPL patients were impaired. High ubiquitination of c-Maf inducing protein (CMIP) was detected in RPL B cells. Exposure to thapsigargin (an ER stress agonist) decreased the amount of CMIP in B cells. The effects of ER stress on reducing CMIP quantity in B cells were mediated by the histone H2B E3 ubiquitin ligase ring finger protein 20 (RNF20). Inhibition of RNF20 or ER stress restored the inducibility of immune regulatory functions of B220⁺ B cells of RPL patients. In summary, peripheral B cells in patients with RPL show impaired immune regulation capacity, in which exacerbated ER stress plays a crucial role. Regulation of ER stress or inhibition of RNF20 can restore the immune regulatory capacity in the B cells.

Keywords: B cell; Endoplasmic reticulum stress; Immune regulation; Interleukin 10; Recurrent pregnancy loss.