Pathogenic autoantibody production requires loss of tolerance against desmoglein 3 in both T and B cells in experimental pemphigus vulgaris

Kazuyuki Tsunoda; Takayuki Ota; Harumi Suzuki; Manabu Ohyama; Tetsuo Nagai; Takeji Nishikawa; Masayuki Amagai; Shigeo Koyasu

doi:10.1002/1521-4141(200203)32:3<627::AID-IMMU627>3.0.CO;2-1

Pathogenic autoantibody production requires loss of tolerance against desmoglein 3 in both T and B cells in experimental pemphigus vulgaris

Eur J Immunol. 2002 Mar;32(3):627-33. doi: 10.1002/1521-4141(200203)32:3<627::AID-IMMU627>3.0.CO;2-1.

Authors

Kazuyuki Tsunoda¹, Takayuki Ota, Harumi Suzuki, Manabu Ohyama, Tetsuo Nagai, Takeji Nishikawa, Masayuki Amagai, Shigeo Koyasu

Affiliation

¹ Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.

PMID: 11857336
DOI: 10.1002/1521-4141(200203)32:3<627::AID-IMMU627>3.0.CO;2-1

Abstract

Mechanisms of tolerance break against desmoglein 3 (Dsg3) in patients with pemphigus vulgaris (PV) producing pathogenic anti-Dsg3 IgG autoantibodies are unclear. In this study, using a novel PV mouse model involving Dsg3 knockout mice, we investigated the mechanisms leading to production of autoantibodies against Dsg3. Adoptive transfer of Dsg3(-/-) splenocytes immunized with recombinant mouse Dsg3 to Rag2(-/-) recipient mice expressing Dsg3 resulted in the stable production of anti-Dsg3 IgG and development of PV phenotypes including oral erosions with suprabasilar acantholysis. When purified T and B cells from Dsg3(-/-), Dsg3(+/-) or Dsg3(+/+) mice were mixed with various combinations and transferred to Rag2(-/-) mice, pathogenic anti-Dsg3 IgG production was observed only with a combination of Dsg3(-/-) T and Dsg3(-/-) B cells but not with the other combinations. These results suggest that loss of tolerance against Dsg3 in both B and T cells is important for the development of autoimmune state of PV.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adoptive Transfer
Animals
Autoantibodies / biosynthesis*
Autoantibodies / immunology
Autoantigens / immunology*
B-Lymphocyte Subsets / immunology*
B-Lymphocyte Subsets / transplantation
Cadherins / immunology*
Cell Line
Crosses, Genetic
DNA-Binding Proteins / genetics
DNA-Binding Proteins / physiology
Desmoglein 3
Disease Models, Animal
Epidermis / pathology
Female
Flow Cytometry
Humans
Immunization
Immunoglobulin G / biosynthesis
Immunoglobulin G / immunology
Keratinocytes / immunology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mouth Mucosa / pathology
Nuclear Proteins
Pemphigus / immunology*
Phenotype
Recombinant Fusion Proteins / immunology
Self Tolerance*
T-Lymphocyte Subsets / immunology*
T-Lymphocyte Subsets / transplantation

Substances

Autoantibodies
Autoantigens
Cadherins
DNA-Binding Proteins
DSG3 protein, human
Desmoglein 3
Immunoglobulin G
Nuclear Proteins
RAG2 protein, human
Rag2 protein, mouse
Recombinant Fusion Proteins
V(D)J recombination activating protein 2