TY - JOUR
T1 - Clonotypic analysis of the antibody response to the acetylcholine receptor in experimental autoimmune myasthenia gravis
AU - Brown, ReneéM M.
AU - Krolick, Keith A.
N1 - Funding Information:
We gratefully acknowledge the technical assistance of Irma Clutter, and Mary Devadoss for her secretarial expertise. This work was supported by grants from the Muscular Dystrophy Association and the National Institutes of Health (NS18938, NS24954).
PY - 1988/9
Y1 - 1988/9
N2 - Autoreactive B cells reactive with the acetylcholine receptor (AChR), and the antibodies produced by them, are proposed to play a primary role in the immunopathology of myasthenia gravis and its animal models. Therefore, the anti-AChR antibody response induced in rats was characterized for the clonotypic heterogeneity, isotype distribution, and affinity by isoelectric focusing (IEF) and affinity immunoblotting. It was determined that the rat anti-AChR serum antibody was relatively heterogeneous, reflecting the oligoclonality of the response. Furthermore, isotypic dominance by IgG2a was observed in that the majority of clonal products detected by IEF were of this isotype in both primary and secondary responses. Lastly, the clonotypic anti-AChR antibodies were of relatively low affinity (avidity) when compared to antibodies reactive with the highly immunogenic protein antigen, keyhole limpet hemocyanin; anti-AChR antibody avidity did not appear to increase when the antibodies in the secondary response were compared to antibodies in the primary response. These antibody characteristics are discussed in terms of their role in disease induction.
AB - Autoreactive B cells reactive with the acetylcholine receptor (AChR), and the antibodies produced by them, are proposed to play a primary role in the immunopathology of myasthenia gravis and its animal models. Therefore, the anti-AChR antibody response induced in rats was characterized for the clonotypic heterogeneity, isotype distribution, and affinity by isoelectric focusing (IEF) and affinity immunoblotting. It was determined that the rat anti-AChR serum antibody was relatively heterogeneous, reflecting the oligoclonality of the response. Furthermore, isotypic dominance by IgG2a was observed in that the majority of clonal products detected by IEF were of this isotype in both primary and secondary responses. Lastly, the clonotypic anti-AChR antibodies were of relatively low affinity (avidity) when compared to antibodies reactive with the highly immunogenic protein antigen, keyhole limpet hemocyanin; anti-AChR antibody avidity did not appear to increase when the antibodies in the secondary response were compared to antibodies in the primary response. These antibody characteristics are discussed in terms of their role in disease induction.
KW - Acetylcholine receptor
KW - Autoantibody
KW - Isoelectric focusing
KW - Myasthenia gravis
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U2 - 10.1016/0165-5728(88)90003-3
DO - 10.1016/0165-5728(88)90003-3
M3 - Article
C2 - 3261738
AN - SCOPUS:0023740007
SN - 0165-5728
VL - 19
SP - 205
EP - 222
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 3
ER -