B lymphocytes are crucial antigen-presenting cells in the pathogenic autoimmune response to GAD65 antigen in nonobese diabetic mice

Marika Falcone, Jae Lee, Gail Patstone, Brian Yeung, Nora Sarvetnick

Research output: Contribution to journalArticle

209 Citations (Scopus)

Abstract

Recent reports have shown that B cells play a key role in the pathogenesis of T cell-mediated autoimmune diseases such as insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic mice (NOD). We have investigated the role of B lymphocytes as APCs in the generation of autoreactive T cell responses by comparing spontaneous responses to self Ags in B cell-deficient and wild-type NOD mice. We determined that B cell- deficient mice had no spontaneous responses to 65-kDa glutamate decarboxylase (GAD65), its immunodominant peptides, and the 60-kDa heat shock protein. In contrast, these Ags are able to induce proliferative responses in the splenocyte cultures of B cell-positive NOD mice. However, T cells from B- deficient mice conserved the ability to respond to nonself Ags and mitogens. The Ag, presenting function of B cells was pivotal in the autoimmune response, since the proliferation of wild-type splenocytes to GAD65 was completely inhibited by blocking the surface Ig-mediated capture of the protein Ag by B cells. Responses to immunodominant GAD65 peptides were also absent in B cell-deficient NOD mice, suggesting that B cells are crucial with regard to the diversification of the autoimmune response to various self epitopes. We believe our results represent strong evidence that B cells are required as APCs to generate pathogenic autoimmune T cell responses and provide a direct correlation between the protection from autoimmune diabetes previously reported in B cell-deficient NOD mice and the lack of anti-GAD65 and anti-heat shock protein 60 T cell responses in these mice.

Original languageEnglish
Pages (from-to)1163-1168
Number of pages6
JournalJournal of Immunology
Volume161
Issue number3
Publication statusPublished - Aug 1 1998

Fingerprint

Inbred NOD Mouse
Antigen-Presenting Cells
Autoimmunity
B-Lymphocytes
Antigens
T-Lymphocytes
Chaperonin 60
Type 1 Diabetes Mellitus
Peptides
Mitogens
Autoimmune Diseases
Epitopes

ASJC Scopus subject areas

  • Immunology

Cite this

B lymphocytes are crucial antigen-presenting cells in the pathogenic autoimmune response to GAD65 antigen in nonobese diabetic mice. / Falcone, Marika; Lee, Jae; Patstone, Gail; Yeung, Brian; Sarvetnick, Nora.

In: Journal of Immunology, Vol. 161, No. 3, 01.08.1998, p. 1163-1168.

Research output: Contribution to journalArticle

Falcone, Marika ; Lee, Jae ; Patstone, Gail ; Yeung, Brian ; Sarvetnick, Nora. / B lymphocytes are crucial antigen-presenting cells in the pathogenic autoimmune response to GAD65 antigen in nonobese diabetic mice. In: Journal of Immunology. 1998 ; Vol. 161, No. 3. pp. 1163-1168.
@article{c947ab70e8be4eaa9a0fa796887217a3,
title = "B lymphocytes are crucial antigen-presenting cells in the pathogenic autoimmune response to GAD65 antigen in nonobese diabetic mice",
abstract = "Recent reports have shown that B cells play a key role in the pathogenesis of T cell-mediated autoimmune diseases such as insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic mice (NOD). We have investigated the role of B lymphocytes as APCs in the generation of autoreactive T cell responses by comparing spontaneous responses to self Ags in B cell-deficient and wild-type NOD mice. We determined that B cell- deficient mice had no spontaneous responses to 65-kDa glutamate decarboxylase (GAD65), its immunodominant peptides, and the 60-kDa heat shock protein. In contrast, these Ags are able to induce proliferative responses in the splenocyte cultures of B cell-positive NOD mice. However, T cells from B- deficient mice conserved the ability to respond to nonself Ags and mitogens. The Ag, presenting function of B cells was pivotal in the autoimmune response, since the proliferation of wild-type splenocytes to GAD65 was completely inhibited by blocking the surface Ig-mediated capture of the protein Ag by B cells. Responses to immunodominant GAD65 peptides were also absent in B cell-deficient NOD mice, suggesting that B cells are crucial with regard to the diversification of the autoimmune response to various self epitopes. We believe our results represent strong evidence that B cells are required as APCs to generate pathogenic autoimmune T cell responses and provide a direct correlation between the protection from autoimmune diabetes previously reported in B cell-deficient NOD mice and the lack of anti-GAD65 and anti-heat shock protein 60 T cell responses in these mice.",
author = "Marika Falcone and Jae Lee and Gail Patstone and Brian Yeung and Nora Sarvetnick",
year = "1998",
month = "8",
day = "1",
language = "English",
volume = "161",
pages = "1163--1168",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - B lymphocytes are crucial antigen-presenting cells in the pathogenic autoimmune response to GAD65 antigen in nonobese diabetic mice

AU - Falcone, Marika

AU - Lee, Jae

AU - Patstone, Gail

AU - Yeung, Brian

AU - Sarvetnick, Nora

PY - 1998/8/1

Y1 - 1998/8/1

N2 - Recent reports have shown that B cells play a key role in the pathogenesis of T cell-mediated autoimmune diseases such as insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic mice (NOD). We have investigated the role of B lymphocytes as APCs in the generation of autoreactive T cell responses by comparing spontaneous responses to self Ags in B cell-deficient and wild-type NOD mice. We determined that B cell- deficient mice had no spontaneous responses to 65-kDa glutamate decarboxylase (GAD65), its immunodominant peptides, and the 60-kDa heat shock protein. In contrast, these Ags are able to induce proliferative responses in the splenocyte cultures of B cell-positive NOD mice. However, T cells from B- deficient mice conserved the ability to respond to nonself Ags and mitogens. The Ag, presenting function of B cells was pivotal in the autoimmune response, since the proliferation of wild-type splenocytes to GAD65 was completely inhibited by blocking the surface Ig-mediated capture of the protein Ag by B cells. Responses to immunodominant GAD65 peptides were also absent in B cell-deficient NOD mice, suggesting that B cells are crucial with regard to the diversification of the autoimmune response to various self epitopes. We believe our results represent strong evidence that B cells are required as APCs to generate pathogenic autoimmune T cell responses and provide a direct correlation between the protection from autoimmune diabetes previously reported in B cell-deficient NOD mice and the lack of anti-GAD65 and anti-heat shock protein 60 T cell responses in these mice.

AB - Recent reports have shown that B cells play a key role in the pathogenesis of T cell-mediated autoimmune diseases such as insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic mice (NOD). We have investigated the role of B lymphocytes as APCs in the generation of autoreactive T cell responses by comparing spontaneous responses to self Ags in B cell-deficient and wild-type NOD mice. We determined that B cell- deficient mice had no spontaneous responses to 65-kDa glutamate decarboxylase (GAD65), its immunodominant peptides, and the 60-kDa heat shock protein. In contrast, these Ags are able to induce proliferative responses in the splenocyte cultures of B cell-positive NOD mice. However, T cells from B- deficient mice conserved the ability to respond to nonself Ags and mitogens. The Ag, presenting function of B cells was pivotal in the autoimmune response, since the proliferation of wild-type splenocytes to GAD65 was completely inhibited by blocking the surface Ig-mediated capture of the protein Ag by B cells. Responses to immunodominant GAD65 peptides were also absent in B cell-deficient NOD mice, suggesting that B cells are crucial with regard to the diversification of the autoimmune response to various self epitopes. We believe our results represent strong evidence that B cells are required as APCs to generate pathogenic autoimmune T cell responses and provide a direct correlation between the protection from autoimmune diabetes previously reported in B cell-deficient NOD mice and the lack of anti-GAD65 and anti-heat shock protein 60 T cell responses in these mice.

UR - http://www.scopus.com/inward/record.url?scp=0032145276&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032145276&partnerID=8YFLogxK

M3 - Article

C2 - 9686575

AN - SCOPUS:0032145276

VL - 161

SP - 1163

EP - 1168

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -