Immunoglobulin gene polymorphisms shape the naïve B-cell receptor repertoire; relevance to celiac disease

IF 4.2 3区医学 Q1 GENETICS & HEREDITY

Genes and immunity Pub Date : 2026-02-26 DOI:10.1038/s41435-026-00384-4

Aengus Officer, Corey T. Watson, Eric Engelbrecht, Shiva Dahal-Koirala, Louise F. Risnes, Knut E. A. Lundin, Eivind Ness-Jensen, Ida Lindeman, Ludvig M. Sollid

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Abstract

Genetic variation in the loci encoding immunoglobulin genes (IGH, IGK and IGL) affects the repertoire of B-cell receptors (BCRs). Such effects were previously demonstrated for total peripheral blood B cells, but so far have not been investigated at scale for isolated naïve B cells. As B cells are implicated in the pathogenesis of autoimmune diseases, genetically encoded features of the naïve BCR repertoire may affect disease risk, for instance in celiac disease (CeD) which is hallmarked by stereotyped disease-specific antibodies that recognize antigen in their germline configuration. Here we have characterized the BCR repertoire of naïve B cells in 102 individuals with CeD and 102 control subjects by undertaking gene usage quantitative trait loci analyses based on repertoire sequencing and single nucleotide polymorphism genotyping. Variants within each of the loci had significant effects on the naïve BCR repertoires, with the usage of 80% of IGH genes, 54% of IGK genes and 84% of IGL genes being significantly affected by gene polymorphisms. Effects of genetic polymorphisms on BCR usage were observed for genes implicated in stereotypic responses previously associated with CeD, yet no strong evidence for CeD predisposing effects of polymorphisms within the IGH, IGK and IGL loci was uncovered.

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免疫球蛋白基因多态性塑造naïve b细胞受体库；与乳糜泻相关。

编码免疫球蛋白基因（IGH， IGK和IGL）的基因座的遗传变异影响b细胞受体（bcr）的库。这种效应先前在整个外周血B细胞中被证实，但到目前为止还没有对分离的naïve B细胞进行大规模研究。由于B细胞与自身免疫性疾病的发病机制有关，naïve BCR库的遗传编码特征可能影响疾病风险，例如在乳糜泻（CeD）中，以识别其种系结构中的抗原的定型疾病特异性抗体为特征。本研究通过基于库测序和单核苷酸多态性基因分型的基因使用数量性状位点分析，对102例CeD患者和102例对照者naïve B细胞的BCR库进行了表征。每个基因座内的变异对naïve BCR谱有显著影响，80%的IGH基因、54%的IGK基因和84%的IGL基因的使用受到基因多态性的显著影响。基因多态性对BCR使用的影响被观察到涉及先前与CeD相关的刻板反应的基因，但没有发现强有力的证据表明在IGH， IGK和IGL位点的多态性对CeD易感性的影响。

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来源期刊

Genes and immunity 医学-免疫学

CiteScore

8.90

自引率

4.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Genes & Immunity emphasizes studies investigating how genetic, genomic and functional variations affect immune cells and the immune system, and associated processes in the regulation of health and disease. It further highlights articles on the transcriptional and posttranslational control of gene products involved in signaling pathways regulating immune cells, and protective and destructive immune responses.