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The datasets used or analysed during the current study are available from the corresponding author on reasonable request.
References
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Funding
This work was supported by the National Key Research and Development Programme of China (grant no: 2017YFC0909002), the National Natural Science Foundation of China (grant no: 81974251) and Shanghai Sailing Program (No. 20YF1425800).
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LL and QF supervised the study and revised the manuscript. RL, RW, JQ and CW performed the experiments. RL, JQ and RW drafted the manuscript. QF collected clinical data. All authors contributed to the article and approved the submitted version.
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The study was approved by the ethics committee of Shanghai Jiao Tong University affiliated Renji Hospital (No. [2017]201). The participants provided their written informed consent to participate in this study.
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The patient referred to our department and age and sex-matched healthy people were recruited into the study with signed informed consent.
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Written informed consent for publication of this paper was obtained from the Shanghai Jiao Tong University affiliated Renji Hospital and all authors.
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Fig. S1 Genetic and family pedigree of the
NFKB1 mutation. (A) The pedigree of the family with the G297* NFKB1 mutation. (B) Schematic structure of NFKB1 (p50/p105) and the corresponding domains, mutation is shown with a vertical bar. (C) Sanger sequencing of the G297* NFKB1 mutation (c.889 G > T). (D-E) Transcription of canonical NF-κB target genes IL-6 (D) and IL-1β (E) of PBMCs from the patient and HCs, cells were stimulated with LPS for 4 h. (F) Impaired B-cell differentiation of the patient. Fluorescence activated cell sorter (FACS) analysis of naive B (IgD+CD27−), MZB-like (IgD+CD27+), class-switched memory B (IgD−CD27+) and double-negative (DN) B (IgD−CD27−) population in the peripheral blood of the patient and HC. (PNG 805 kb)
Fig. S2 Expression of CD127 (A) and CXCR5 (B) on total T cells in the affected patient and unrelated healthy controls.
Total T cells and expression of CXCR5 and CD127 on T cells were measured using flow cytometry. (PNG 404 kb)
Fig. S3
NFKB1 and expression of CXCR5 on Human T cells. (A) Total human CD8 + T cells were sorted using anti-CD8 nano-beads and infected with lentivirus expressing a NFKB1 shRNA tagged with EGFP (LV-NFKB1-shRNA-EGFP) to knock-down NFKB1 or empty vector (LV-con-shRNA-EGFP) for 72 h. (B) T cells infected for 72 h were treated with PBS or anti-CD3/CD28 or PMA/Ionomycin as indicated for 48 h. The expression of CXCR5 was measured by flow cytometry. (C) The efficiency of NFKB1 knock-down after 72 h of the lentivirus infection was determined by western-blot analysis. Data is representative of three independent experiments. (PNG 478 kb)
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Li, R., Qian, J., Wang, R. et al. Identification of a Novel Nonsense Mutation in NFKB1 Causing Common Variable Immunodeficiency with Decreased Tfh Cells. J Clin Immunol 43, 1784–1787 (2023). https://doi.org/10.1007/s10875-023-01588-3
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DOI: https://doi.org/10.1007/s10875-023-01588-3