常见变异型免疫缺陷病患者CD27(+) B细胞上STAT3磷酸化增加。

Increased STAT3 phosphorylation on CD27(+) B-cells from common variable immunodeficiency disease patients.

作者信息

Clemente Antonio, Pons Jaume, Lanio Nallibe, Cunill Vanesa, Frontera Guillem, Crespí Catalina, Matamoros Núria, Ferrer Joana M

机构信息

Fundació d'Investigació Sanitària de les Illes Balears (FISIB), Hospital Universitari Son Espases, Palma de Mallorca, Spain; Institut d'Investigació Sanitària de Palma (IdISPa), Hospital Universitari Son Espases, Palma de Mallorca, Spain.

Institut d'Investigació Sanitària de Palma (IdISPa), Hospital Universitari Son Espases, Palma de Mallorca, Spain; Immunology Department, Hospital Universitari Son Espases, Palma de Mallorca, Spain.

出版信息

Clin Immunol. 2015 Dec;161(2):77-88. doi: 10.1016/j.clim.2015.09.004. Epub 2015 Sep 7.

DOI:10.1016/j.clim.2015.09.004

PMID:26360251

Abstract

Maturation and differentiation of B-cells are driven by T-cells' help through IL-21/STAT3 axis in GC centers or through extrafollicular pathways, in a T-independent manner. B-cell differentiation is defective in common variable immunodeficiency disease (CVID) patients. We investigated if IL-21/STAT3 axis alterations could influence B-cell fate. We activated purified CVID B-cells with surrogate T-dependent (anti-CD40), T-independent (TLR-9 ligand) stimuli or through B-cell receptor engagement (anti-IgM) with or without IL-21. IL-21 mediated STAT3 activation was greater on CD27(-) than CD27(+) B-cells depending on the stimulus. IL-21 alone induced STAT3 phosphorylation (pSTAT3) only on CD27(-) B-cells and IL-21 induced higher pSTAT3 levels on CD27(-) than CD27(+) B-cells after anti-IgM or anti-CD40 activation. CVID CD27(+) B-cells showed selective STAT3 hyperphosphorylation after activation with anti-IgM or anti-CD40 alone and anti-IgM, anti-CD40 or ODN combined with IL-21. Increased STAT3 activation during immune responses could result in B-cell differentiation defects in CVID.

摘要

在生发中心，B细胞的成熟和分化由T细胞通过IL-21/STAT3轴提供帮助驱动，或通过非依赖T细胞的滤泡外途径实现。在常见变异型免疫缺陷病（CVID）患者中，B细胞分化存在缺陷。我们研究了IL-21/STAT3轴的改变是否会影响B细胞命运。我们用替代T细胞依赖（抗CD40）、T细胞非依赖（TLR-9配体）刺激或通过B细胞受体结合（抗IgM）激活纯化的CVID B细胞，并添加或不添加IL-21。根据刺激的不同，IL-21介导的STAT3激活在CD27(-) B细胞上比在CD27(+) B细胞上更强。单独的IL-21仅在CD27(-) B细胞上诱导STAT3磷酸化（pSTAT3），并且在抗IgM或抗CD40激活后，IL-21在CD27(-) B细胞上诱导的pSTAT3水平高于CD27(+) B细胞。CVID CD27(+) B细胞在用单独的抗IgM或抗CD40以及抗IgM、抗CD40或ODN与IL-21联合激活后，显示出选择性的STAT3过度磷酸化。免疫反应期间STAT3激活增加可能导致CVID中的B细胞分化缺陷。