| Title: |
Failure of B Cell Tolerance in CVID |
| Authors: |
Christopher T. Richardson, Maria A. Slack, Gitika Dhillon, Carolina Z. Marcus, Jennifer Barnard, Arumugam Palanichamy, Ignacio Sanz, Richard John Looney, Jennifer H. Anolik |
| Source: |
Frontiers in Immunology, Vol 10 (2019) |
| Publisher Information: |
Frontiers Media S.A., 2019. |
| Publication Year: |
2019 |
| Collection: |
LCC:Immunologic diseases. Allergy |
| Subject Terms: |
CVID, common variable immunodeficiency disorders, autoimmunity, B cell, B cell subpopulations, B cell tolerance, Immunologic diseases. Allergy, RC581-607 |
| More Details: |
Common variable immunodeficiency (CVID) comprises a group of related disorders defined by defects in B cell function and antibody production. Concurrent autoimmune features are common, but the underlying pathogenic mechanisms of autoimmunity in CVID are poorly understood. Overlap in some clinical and laboratory features suggests a shared pathogenesis, at least in part, with systemic lupus erythematosus (SLE). One important part of SLE pathogenesis is loss of B cell tolerance, an aspect that warrants further study in CVID. The study of inherently autoreactive 9G4+ B cells has led to a greater understanding of B cell tolerance defects in lupus. Study of these B cells in CVID has yielded conflicting results, largely due to differences in methodological approaches. In this study, we take a comprehensive look at 9G4+ B cells throughout B cell development in CVID patients and compare patients both with and without autoimmune features. Using flow cytometry to examine B cell subpopulations in detail, we show that only those CVID patients with autoimmune features demonstrate significant expansion of 9G4+ B cells, both in naïve and multiple memory populations. Examination of two autoreactive B cell subsets recently characterized in SLE, the activated naïve (aNAV) and double negative 2 (DN2) B cells, reveals an expanded 9G4+ DN2 population to be common among CVID patients. These results reveal that both multiple central and peripheral B cell tolerance defects are related to autoimmunity in CVID. Furthermore, these data suggest that the autoreactive DN2 B cell population, which has not previously been examined in CVID, may play an important role in the development of autoimmunity in patients with CVID. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1664-3224 |
| Relation: |
https://www.frontiersin.org/article/10.3389/fimmu.2019.02881/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2019.02881 |
| Access URL: |
https://doaj.org/article/4ae23bd982c148938e5b3bb8d5b71290 |
| Accession Number: |
edsdoj.4ae23bd982c148938e5b3bb8d5b71290 |
| Database: |
Directory of Open Access Journals |
