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.

• Authors: M Falcone, J Lee, G Patstone, B Yeung, N Sarvetnick
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 161 Issue 3 Pg. 1163-8 (Aug 01 1998) ISSN: 0022-1767 [Print] United States
• PMID: 9686575 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Blocking
• Autoantigens
• Epitopes
• Peptide Fragments
• Receptors, Antigen, B-Cell
• Glutamate Decarboxylase

Topics

• Animals
• Antibodies, Blocking (pharmacology)
• Antigen-Presenting Cells (enzymology, immunology)
• Autoantigens (administration & dosage, immunology)
• B-Lymphocytes (enzymology, immunology, metabolism)
• Diabetes Mellitus, Type 1 (enzymology, etiology, immunology)
• Epitopes
• Glutamate Decarboxylase (immunology)
• Immunity, Cellular
• Islets of Langerhans (immunology)
• Lymphocyte Activation
• Lymphocyte Depletion
• Mice
• Mice, Inbred NOD
• Mice, Knockout
• Peptide Fragments (administration & dosage, immunology)
• Receptors, Antigen, B-Cell (immunology, physiology)
• T-Lymphocyte Subsets (immunology)