Evidence map›Paper›PMID 39405181›Full record

ArticleClinical and experimental immunology2025

Intrinsic functional defects in B cells of patients with NFKB2 mutations.

Qing Min, Yaxuan Li, Xuzhe Wu, Meiping Yu, Wenjing Ying, Qinhua Zhou, Jia Hou, Bijun Sun, Xiaoying Hui, Lulu Dong and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical and experimental immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Qing MinDepartment of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Yaxuan LiDepartment of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Xuzhe WuDepartment of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Meiping YuDepartment of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Wenjing YingDepartment of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Qinhua ZhouDepartment of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Jia HouDepartment of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Bijun SunDepartment of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Xiaoying HuiDepartment of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Lulu DongDepartment of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Xin MengDepartment of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Hai ZhangDepartment of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Ziying HuDepartment of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Xiaoqian FengDepartment of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Jinqiao SunDepartment of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Wenjie WangDepartment of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Xiaochuan WangDepartment of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Ji-Yang WangDepartment of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.ORCID 0000-0003-3038-3826

Funding

China Postdoctoral Science Foundation Grant 2022M720782National Natural Science Foundation for Young Scholar 82202013National Natural Science Foundation of China 32330033Shanghai Municipal Science and Technology Major Project ZD2021CY001
6 · The paper itself

Abstract

Mutations in the human nuclear factor-κB2 gene (NFKB2) are associated with common variable immunodeficiency (CVID) or combined immunodeficiency diseases (CID), characterized by B-cell lymphopenia, hypogammaglobulinemia, and T-cell dysfunction. This study investigated whether B cells with NFKB2 mutations exhibit intrinsic impairments in activation, class-switch recombination, and differentiation. We analyzed five patients from four unrelated families with CVID, each carrying a heterozygous NFKB2 mutation: P1 (C.2595_2614del, p.A867Gfs*12), P2 (C.2597G > A, p.S866N), P3 (C.2540dupT, p.R848Efs*38), and P4 and P5 (C.2570_2571insCAGCACA, p.A860Qfs*28). The patients with frameshift mutations (P1, P3, P4, and P5) exhibited truncated proteins detectable in their peripheral blood mononuclear cells, while P2 had a missense mutation. All identified mutations disrupted the processing of p100 into the active p52 form, resulting in NF-κB2 loss of function and IκBδ gain of function. Clinically, P1, P2, and P3 exhibited B-cell lymphopenia, and all five patients presented with hypogammaglobulinemia. Notably, P2 exhibited a markedly low B-cell count, associated with increased proportions of memory B and IgD-CD27- double-negative B cells. In vitro experiments with naïve B cells from P1 and P4 demonstrated decreased survival, impaired activation, and reduced differentiation into CD27+IgD- cells and plasmablasts, while class-switch recombination was unaffected. These findings reveal novel B-cell intrinsic functional defects in patients with NFKB2 mutations.

Indexed as

B-LymphocytesCommon Variable ImmunodeficiencyMutationNF-kappa B p52 SubunitAdolescentAdultCell DifferentiationChildFemaleFrameshift MutationHumansImmunoglobulin Class SwitchingLymphocyte ActivationMaleNF-kappa B p52 SubunitNFKB2 protein, humanB-cell differentiationclass-switch recombinationCVIDNFKB2

Identifiers

PMID39405181
PMCPMC11773609

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.