論文 - 詳細
| RRC ID | 68420 |
|---|---|
| 著者 | Min Q, Meng X, Zhou Q, Wang Y, Li Y, Lai N, Xiong E, Wang W, Yasuda S, Yu M, Zhang H, Sun J, Wang X, Wang JY. |
| タイトル | RAG1 splicing mutation causes enhanced B cell differentiation and autoantibody production. |
| ジャーナル | JCI Insight |
| Abstract |
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. |
| 巻・号 | 6(19) |
| 公開日 | 2021-10-8 |
| DOI | 10.1172/jci.insight.148887 |
| PII | 148887 |
| PMID | 34622798 |
| PMC | PMC8525647 |
| MeSH | Autoantibodies / immunology* Autoimmune Diseases / genetics* Autoimmune Diseases / immunology Autoimmune Diseases / therapy B-Lymphocytes / immunology* Child Cord Blood Stem Cell Transplantation Fatal Outcome Granuloma / genetics* Granuloma / immunology Granuloma / therapy Homeodomain Proteins / genetics* Homeodomain Proteins / metabolism Homozygote Humans Immunoglobulin G / immunology Immunoglobulin M / immunology Immunologic Deficiency Syndromes / genetics* Immunologic Deficiency Syndromes / immunology Immunologic Deficiency Syndromes / therapy Immunologic Memory / immunology Lymphopenia / genetics Lymphopenia / immunology Lymphopoiesis / genetics* Lymphopoiesis / immunology Male Plasma Cells / immunology RNA Splice Sites / genetics Receptors, Antigen, B-Cell / immunology* V(D)J Recombination / genetics |
| IF | 6.205 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | NALM-6(RCB1933) |