Hspa13 Promotes Plasma Cell Production and Antibody Secretion

Frontiers in Immunology

Ruonan Xu¹  Renxi Wang¹  Bing Zhai²  Youdi He³  Ying Fang⁴  Ning Ma⁴  Chunmei Hou⁵  Chen Xing⁵  Gencheng Han⁵  Xiaoqian Wang⁶  Guojiang Chen⁷  He Xiao⁷ 

[1] Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China;Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing, China;Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China;Department of Rheumatology, First Hospital of Jilin University, Changchun, China;Institute of Military Cognition and Brain Sciences, Beijing, China;Staidson (Beijing) Biopharmaceuticals Co., Ltd, Beijing, China;State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Beijing, China;

关键词: Hspa13;    SLE;    B cells;    plasma cells;    antibody;   

DOI  :  10.3389/fimmu.2020.00913

来源: DOAJ

【 摘 要 】

The generation of large numbers of plasma cells (PCs) is a main factor in systemic lupus erythematosus (SLE). We hypothesize that Hspa13, a member of the heat shock protein family, plays a critical role in the control of PC differentiation. To test the hypothesis, we used lipopolysaccharide (LPS)-activated B cells and a newly established mouse line with a CD19cre-mediated, B cell–specific deletion of Hspa13: Hspa13 cKO mice. We found that Hspa13 mRNA was increased in PCs from atacicept-treated lupus-prone mice and in LPS-stimulated plasmablasts (PBs) and PCs. A critical finding was that PBs and PCs [but not naïve B cells and germinal center (GC) B cells] expressed high levels of Hspa13. In contrast, the Hspa13 cKO mice had a reduction in BPs, PCs, and antibodies induced in vitro by LPS and in vivo by sheep red blood cells (SRCs)- or 4-hydroxy-3-nitrophenylacetyl (NP)-immunization. Accordingly, the Hspa13 cKO mice had reduced class-switched and somatically hypermutated antibodies with defective affinity maturation. Our work also showed that Hspa13 interacts with proteins (e.g., Bcap31) in the endoplasmic reticulum (ER) to positively regulate protein transport from the ER to the cytosol. Importantly, Hspa13 mRNA was increased in B220+ cells from patients with multiple myeloma (MM) or SLE, whereas Hspa13 cKO led to reduced autoantibodies and proteinuria in both pristane-induced lupus and lupus-prone MRL/lpr mouse models. Collectively, our data suggest that Hspa13 is critical for PC development and may be a new target for eliminating pathologic PCs.

【 授权许可】

Unknown