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

213 Scopus citations

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 (US)
Pages (from-to)1163-1168
Number of pages6
JournalJournal of Immunology
Volume161
Issue number3
StatePublished - Aug 1 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'B lymphocytes are crucial antigen-presenting cells in the pathogenic autoimmune response to GAD65 antigen in nonobese diabetic mice'. Together they form a unique fingerprint.

  • Cite this