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Ig gene analysis reveals altered selective pressures on Ig-producing cells in parotid glands of primary Sjögren's syndrome patients
Journal article   Open access   Peer reviewed

Ig gene analysis reveals altered selective pressures on Ig-producing cells in parotid glands of primary Sjögren's syndrome patients

Nishath Hamza, Uri Hershberg, Cees G M Kallenberg, Arjan Vissink, Frederik K L Spijkervet, Hendrika Bootsma, Frans G M Kroese and Nicolaas A Bos
The Journal of immunology (1950), v 194(2), pp 514-521
15 Jan 2015
DOI: https://doi.org/10.4049/jimmunol.1302644
PMID: 25488989
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.4049/jimmunol.1302644View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open

Abstract

Adult Aged Base Sequence Cell Proliferation - genetics Female Humans Immunoglobulin A - genetics Immunoglobulin A - immunology Immunoglobulin G - genetics Immunoglobulin G - immunology Immunoglobulin Heavy Chains - genetics Immunoglobulin Heavy Chains - immunology Immunoglobulin Variable Region - genetics Immunoglobulin Variable Region - immunology Middle Aged Molecular Sequence Data Parotid Gland - immunology Parotid Gland - pathology Sjogren's Syndrome - genetics Sjogren's Syndrome - immunology Sjogren's Syndrome - pathology
In this study, we sought to understand the selective pressures shaping the Ig-producing cell repertoire in the parotid glands of primary Sjögren's syndrome (pSS) patients before and after rituximab treatment (RTX). In particular, we evaluated the role of potential N-glycosylation motifs acquired by somatic hypermutation (ac-Nglycs) within Ig H chain V region (IGHV) genes as alternative selective pressures for B cells in pSS. Five pSS patients received RTX. Sequential parotid salivary gland biopsies were taken before RTX, at 12 wk and at 36-52 wk after treatment. Parotid biopsies from four non-pSS patients served as controls. Sequence analysis was carried out on the IgA and IgG RNA transcripts expressing IGHV3 genes in all parotid biopsies. Both IgG and IgA sequences from pSS patients exhibited no evidence for positive Ag-driven selection pressure in their CDRs in contrast to non-pSS controls. The prevalence of IgG sequences with ac-Nglycs was significantly higher in pSS patients than in non-pSS controls. Selection pressures shaping the IgG and IgA repertoire within pSS patients' parotid glands are distinct from those in non-pSS controls, with very little evidence for positive (auto)antigen selection. The higher prevalence of ac-Nglycs on pSS-IgG compared with non-pSS IgG indicates that ac-Nglycs could be an alternative form of selection pressure. We speculate that B cell hyperproliferation within parotid glands of pSS patients may result from Ag-independent interactions such as that between glycosylated B cell receptors and lectins within the microenvironment rather than (auto)antigen-specific stimulation. Our study brings a new perspective into research on pSS.

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Web of Science research areas
Immunology
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