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Arthritis Research & Therapy

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Open Access 01-12-2017 | Research article

B cell epitope of human cytomegalovirus phosphoprotein 65 (HCMV pp65) induced anti-dsDNA antibody in BALB/c mice

Authors: Ao HoHsieh, Chin Man Wang, Yeong-Jian Jan Wu, Albert Chen, Ming-I Chang, Ji-Yih Chen

Published in: Arthritis Research & Therapy | Issue 1/2017

Abstract

Background

HCMV phosphoprotein 65 (HCMVpp65) is a putative immunogen that acts as an accelerator, inducing autoantibody and exacerbating autoimmune response in susceptible animals. The immunity to pp65_336-439 instigates autoimmunity, suggesting that pp65_336-439 contains crucial B cell epitope(s) for the development of nephritis. This study narrowed down the target epitope to pp65_422-439 for immunization of BALB/c mice and mapping of B cell epitope.

Methods

The target epitope pp65_422-439 reactivity and B cell epitope mapping was examined in serum from pp65_422-439-immunized mice and patients with systemic lupus erythematosus (SLE). Kidney tissue from immunized mice was examined for signs of immune complex nephritis.

Results

Anti-pp65_422-439 antibody in serum either from patients with SLE or from pp65_422-439-immunized mice exhibited cross-reactivity to several nuclear components such as double-stranded DNA (dsDNA). Moreover, the pp65_422-439-immunized mice developed initial signs of glomerulonephritis such as deposition of immunoglobulin G/M (IgG/IgM) and third complement component (C3). With B cell epitope mapping by pp65_422-439-derived decapeptides, one dominant epitope, pp65_428-437, was identified in serum from pp65_422-439-immunized mice and patients with SLE with anti-pp65_422-439 antibody. Epitope spreading from pp65_428-437 to pp65_430-439 was found in pp65_422-439-immunized mice in which we generated monoclonal antibodies to pp65_425-434 and pp65_430-439. However, dsDNA positive reactivity was exclusively observed in Crithidia luciliae stains with pp65_430-439-reactive monoclonal antibody. Additionally, we observed the amelioration of autoimmunity following the elevation of IgM targeting pp65_428-437.

Conclusions

Our data suggest that pp65_428-437 may be an autoimmune or lupus-prone B cell epitope and may catalyze further epitope spreading for inducing autoantibodies in lupus-susceptible individuals.

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Title: B cell epitope of human cytomegalovirus phosphoprotein 65 (HCMV pp65) induced anti-dsDNA antibody in BALB/c mice
Authors: Ao HoHsieh
Chin Man Wang
Yeong-Jian Jan Wu
Albert Chen
Ming-I Chang
Ji-Yih Chen
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Arthritis Research & Therapy / Issue 1/2017
Electronic ISSN: 1478-6362
DOI: https://doi.org/10.1186/s13075-017-1268-2

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B cell epitope of human cytomegalovirus phosphoprotein 65 (HCMV pp65) induced anti-dsDNA antibody in BALB/c mice

Abstract

Background

Methods

Results

Conclusions

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Abstract

Background

Methods

Results

Conclusions

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