ACh receptor protein drives primary and memory autoantibody responses in chimeric human-SCID mice.
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-alpha1-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-alpha1-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.
Yoshikawa
Hiroaki
H
Department of Immunology, Mayo Graduate School and Medical School, Mayo Clinic, Rochester, MN 55905, USA.
Lennon
Vanda A
VA
D000293:Adolescent; D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology; D002678:Chimera / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009132:Muscles / Q000276:immunology*; D009157:Myasthenia Gravis / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D001323:Autoantibodies; D007074:Immunoglobulin G; D011950:Receptors, Cholinergic; D011994:Recombinant Proteins