Clonal B cells in patients with hepatitis C virus–associated mixed cryoglobulinemia contain an expanded anergic CD21low B-cell subset

Author:

Charles Edgar D.12,Brunetti Claudia13,Marukian Svetlana1,Ritola Kimberly D.1,Talal Andrew H.2,Marks Kristen2,Jacobson Ira M.2,Rice Charles M.1,Dustin Lynn B.1

Affiliation:

1. Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, Rockefeller University, New York, NY;

2. Department of Medicine, Division of Gastroenterology and Hepatology, Weill Medical College of Cornell University, New York, NY; and

3. University of Bari, Bari, Italy

Abstract

Abstract Hepatitis C virus (HCV) is associated with the B-cell lymphoproliferative disorders mixed cryoglobulinemia (MC) and non-Hodgkin lymphoma. We have previously reported that HCV+MC+ patients have clonal expansions of hypermutated, rheumatoid factor–bearing marginal zone-like IgM+CD27+ peripheral B cells using the VH1-69 gene. Here we coupled transcriptional profiling with immunophenotypic and functional studies to ascertain these cells' role in MC pathogenesis. Despite their fundamental role in MC disease, these B cells have overall transcriptional features of anergy and apoptosis instead of neoplastic transformation. Highly up-regulated genes include SOX5, CD11C, galectin-1, and FGR, similar to a previously described FCRL4+ memory B-cell subset and to an “exhausted,” anergic CD21low memory B-cell subset in HIV+ patients. Moreover, HCV+MC+ patients' clonal peripheral B cells are enriched with CD21low, CD11c+, FCRL4high, IL-4Rlow memory B cells. In contrast to the functional, rheumatoid factor–secreting CD27+CD21high subset, the CD27+CD21low subpopulation exhibits decreased calcium mobilization and does not efficiently differentiate into rheumatoid factor–secreting plasmablasts, suggesting that a large proportion of HCV+MC+ patients' clonally expanded peripheral B cells is prone to anergy and/or apoptosis. Down-regulation of multiple activation pathways may represent a homeostatic mechanism attenuating otherwise uncontrolled stimulation of circulating HCV-containing immune complexes. This study was registered at www.clinicaltrials.gov as #NCT00435201.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Cited by 167 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

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