Defective Toll-Like Receptors Driven B Cell Response in Hyper IgE Syndrome Patients With STAT3 Mutations.

Ruolan Gong,Jing Wu,Yingying Jin,Tongxin Chen

doi:10.3389/fped.2021.738799

Abstract

Autosomal dominant hyper-IgE syndrome (AD-HIES) is a rare inherited primary immunodeficient disease (PIDs), which is caused by STAT3 gene mutations. Previous studies indicated a defective Toll-like receptor (TLR) 9-induced B cell response in AD-HIES patients, including proliferation, and IgG production. However, the other TLRs-mediated B cell responses in AD-HIES patients were not fully elucidated. In this study, we systematically studied the B cell response to TLRs signaling pathways in AD-HIES patients, including proliferation, activation, apoptosis, cytokine, and immunoglobulin production. Our results showed that the TLRs-induced B cell proliferation and activation was significantly impaired in AD-HIES patients. Besides, AD-HIES patients had defects in TLRs-induced B cell class switch, as well as IgG/IgM secretion and IL-10 production in B cells. Taken together, we first systematically reported the deficiency of TLRs driven B cell response in AD-HIES patients, which help to have a better understanding of the pathology of AD-HIES.

Highlights

Hyper-IgE syndrome (HIES) is a kind of rare inherited primary immunodeficient disease (PIDs), which is characterized by elevated IgE levels, eczema, recurrent infections, and pneumonia
To investigate the Toll-like receptor (TLR)-induced B cell proliferation in Autosomal dominant hyper-IgE syndrome (AD-HIES) patients, CFSE labeled peripheral blood mononuclear cells (PBMCs) from autosomal dominant (AD)-HIES patients and age-matched healthy controls were stimulated with R848 or CpG
The decreased memory B cells reported in AD-HIES patients throw light on the role of signal transduction and activators of transcription 3 (STAT3) in B cell development and function

Summary

Introduction

Hyper-IgE syndrome (HIES) is a kind of rare inherited primary immunodeficient disease (PIDs), which is characterized by elevated IgE levels, eczema, recurrent infections, and pneumonia. Both autosomal dominant (AD) and autosomal recessive (AR) modes of inheritance were reported in the patients with HIES, of which AD-HIES was the most common form. Signal transduction and activators of transcription 3, which belongs to the signal transducer and activator of transcription (STAT) family of signal responsive transcription factors, was Defective B Cell Response in AD-HIES Patients reported to be involved in multiple biological functions, including cell proliferation, inflammation, differentiation, and survival. AD-HIES patients were reported to have reduced neutrophil chemotaxis and function, defective development and maintenance of T cell memory, reduced Th17 cells, reduced memory B cells, defective IL-10 and IL-21 signaling [3]

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