| Title: |
RAG1 splicing mutation causes enhanced B cell differentiation and autoantibody production |
| Authors: |
Qing Min, Xin Meng, Qinhua Zhou, Ying Wang, Yaxuan Li, Nannan Lai, Ermeng Xiong, Wenjie Wang, Shoya Yasuda, Meiping Yu, Hai Zhang, Jinqiao Sun, Xiaochuan Wang, Ji-Yang Wang |
| Source: |
JCI Insight, Vol 6, Iss 19 (2021) |
| Publisher Information: |
American Society for Clinical investigation, 2021. |
| Publication Year: |
2021 |
| Collection: |
LCC:Medicine |
| Subject Terms: |
Autoimmunity, Immunology, Medicine |
| More Details: |
Hypomorphic RAG1 or RAG2 mutations cause primary immunodeficiencies and can lead to autoimmunity, but the underlying mechanisms are elusive. We report here a patient carrying a c.116+2T>G homozygous splice site mutation in the first intron of RAG1, which led to aberrant splicing and greatly reduced RAG1 protein expression. B cell development was blocked at both the pro-B to pre-B transition and the pre-B to immature B cell differentiation step. The patient B cells had reduced B cell receptor repertoire diversity and decreased complementarity determining region 3 lengths. Despite B cell lymphopenia, the patient had abundant plasma cells in the BM and produced large quantities of IgM and IgG Abs, including autoantibodies. The proportion of naive B cells was reduced while the frequency of IgD–CD27– double-negative (DN) B cells, which quickly differentiated into Ab-secreting plasma cells upon stimulation, was greatly increased. Immune phenotype analysis of 52 patients with primary immunodeficiency revealed a strong association of the increased proportion of DN B and memory B cells with decreased number and proportion of naive B cells. These results suggest that the lymphopenic environment triggered naive B cell differentiation into DN B and memory B cells, leading to increased Ab production. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2379-3708 |
| Relation: |
https://doaj.org/toc/2379-3708 |
| DOI: |
10.1172/jci.insight.148887 |
| Access URL: |
https://doaj.org/article/45e62efa5e7f4f46860d57d96cda425f |
| Accession Number: |
edsdoj.45e62efa5e7f4f46860d57d96cda425f |
| Database: |
Directory of Open Access Journals |
