Experimental autoimmune myasthenia gravis induction in B cell-deficient mice

Abstract

Experimental autoimmune myasthenia gravis (EAMG) is an animal model for human myasthenia gravis (MG). Autoantibody-induced functional loss of nicotinic acetylcholine receptor (AChR) at the postsynaptic membrane is an important pathogenic feature of both MG and EAMG. To evaluate the extent at which the humoral immune response against AChR operates in the pathogenesis of EAMG, we immunized B cell knockout (μMT) and wild-type C57BL/6 mice with AChR and complete Freund's adjuvant. The ability of AChR-primed lymph node cells to proliferate and secrete IFN-γ in response to AChR and its dominant peptide α146-162 were intact in μMT mice as in wild-type mice. Similar amounts of mRNA for IFN-γ, IL-4 and IL-10 in AChR-reactive lymph node cells were detected in μMT and wild-type mice. However, μMT mice had no detectable anti-AChR antibodies and remained completely free from clinical EAMG. We conclude that B cells are critically required for the genesis of clinical EAMG, but not for AChR-specific T cell priming.