ACh receptor protein drives primary and memory autoantibody responses in chimeric human-SCID mice

Hiroaki Yoshikawa, Vanda A. Lennon

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

The native antigen that drives the T-helper cells regulating production of muscle acetylcholine receptor (AChR) autoantibodies is unknown. Human T cell lines activated by autoantigens in vitro are of unproven relevance to B cell help. Here we report the functional interaction and unprecedented longevity of AChR-specific human T and B lymphocytes residing in SCID mice. Lymphoid cells from myasthenia gravis (MG) patients and healthy subjects were injected ip. Recombinant human AChR-α1-subunit-1-210 was injected after day 75. Human AChR-specific Ig was produced rapidly in MG-SCID mice challenged once. Only 1 of 32 control hu-SCID mice produced AChR-specific Ig. This required multiple immunizations, was initially cross-reactive with Torpedo AChR, and had a slow course. Thus, memory T and B lymphocytes specific for human AChR-α1-subunit are readily demonstrable in MG patients, interact to produce autoantibody of the same restricted specificity found in the donor's serum, and are long-lived without exogenous autoantigen challenge. In healthy subjects, AChR-specific lymphocytes are infrequent and exhibit naive response characteristics, including apparent affinity maturation of Ig specificity.

Original languageEnglish (US)
Pages (from-to)128-137
Number of pages10
JournalClinical Immunology
Volume104
Issue number2
DOIs
StatePublished - Aug 2002

Keywords

  • Muscle autoantibody
  • Myasthenia gravis
  • Thymic lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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