Increased plasmablasts enhance T cell-mediated beta cell destruction and promote the development of type 1 diabetes

Author:

Ling Qing,Shen Lei,Zhang Wei,Qu DuoDuo,Wang Hongdong,Wang Bin,Liu Yong,Lu Jing,Zhu Dalong,Bi YanORCID

Abstract

AbstractBackgroundAlthough type 1 diabetes (T1D) is typically described as a T cell-mediated autoimmune disease, increasing evidence for a role of B cells has emerged. However, the pivotal disease-relevant B cell subset and its contribution to islet autoimmunity remain elusive.MethodsThe frequencies and phenotypic characteristics of circulating B cell subsets were analyzed using flow cytometry in individuals with new-onset T1D, long-term T1D, type 2 diabetes, and nondiabetic controls, and also in a prospective cohort of patients receiving mesenchymal stromal cell (MSC) transplantation. NOD mice and adoptive transfer assay were used to dissect the role of the certain B cell subset in disease progression. An in-vitro coculture system of islets with immune cells was established to examine the response against islets and the underlying mechanisms.ResultsWe identified that plasmablasts, a B cell subset at the antibody-secreting stage, were significantly increased and correlated with the deterioration of beta cell function in patients with new-onset T1D. Further, a fall of plasmablast number was associated with the preservation of beta cell function in patients who received MSC transplantation after 3 months of follow-up. Meanwhile, a gradual increase of plasmablasts in pancreatic lymph nodes during the natural progression of insulitis was observed in non-obese diabetic (NOD) mice; adoptive transfer of plasmablasts together with T cells from NOD mice accelerated diabetes onset in NOD/SCID recipients.ConclusionsOur study revealed that plasmablasts may function as antigen-presenting cells and promote the activation and proinflammatory response of CD4+T cells, further contributing to the T cell-mediated beta cell destruction. Our results provide insights into the pathogenic role of plasmablasts in islet autoimmunity and may offer new translational strategies for inhibiting T1D development.

Funder

The study was sponsored by grants from the National Key Research and Development Program of China

Nanjing Health Youth Talent

Jiangsu Provincial Key Medical Discipline

Publisher

Springer Science and Business Media LLC

Subject

Genetics (clinical),Genetics,Molecular Biology,Molecular Medicine

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3