The effect of B cell deficiency on the immune response to acetylcholine receptor and the development of experimental autoimmune myasthenia gravis

Vinesh Dedhia, Elzbieta Goluszko, Bo Wu, Caishu Deng, Premkumar Christadoss

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

To study the involvement of B cells in the immune response to acetylcholine receptor (AChR), B-cell-deficient (μ mutant) and control wild- type C57BL/6 mice were immunized with AChR and assessed for clinical and immunopathological manifestations of experimental autoimmune myasthenia gravis (EAMG). The μ mutant mice failed to generate anti-AChR antibodies and were completely resistant to the induction of EAMG. However, μ mutant mice developed clinical EAMG when antibodies to the AChR main immunogenic region were passively transferred. Further, the in vivo expansion of lymph node cells after AChR immunization was greatly impaired in μ mutant mice. The μ mutant mice gave an effective in vitro T cell immune response to the immunodominant pathogenic AChR α chain peptide 146-162 (α146-162) and to the whole AChR protein when tested on day 90 after immunization with AChR, whereas the response to both AChR and its α146-162 peptide was reduced when tested on day 7 after immunization. The in vitro production of IFN-γ and IL- 2 by AChR-specific and α146-162 peptide-specific lymphocytes was lower in μ mutant mice. The AChR immune μ mutant T cells proliferated and produced IFN- γ when AChR or α146-162 peptide was presented by wild-type irradiated AChR- primed antigen-presenting cells (APCs). This indicates that B cells are important in the processing and presentation of AChR dominant peptide in vitro during the initial immune response to AChR. However, APCs of non-B- cell lineage are sufficient to process AChR and prime the T cells to AChR dominant T cell epitope peptides.

Original languageEnglish (US)
Pages (from-to)266-275
Number of pages10
JournalClinical Immunology and Immunopathology
Volume87
Issue number3
DOIs
StatePublished - Jun 1998

Keywords

  • Antigen presentation
  • B cells
  • Immune response
  • Myasthenia gravis
  • μ gene knockout

ASJC Scopus subject areas

  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Immunology

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