Recall immune memory: a new tool for generating late onset autoimmune myasthenia gravis.
Most patients with autoimmune myasthenia gravis (MG) produce autoantibodies against their muscle acetylcholine receptors (AChR), causing debilitating muscle weakness. Approximately 60% of MG patients first exhibit myasthenic symptoms after the age of 40. Yet, in the C57BL/6 mouse model of MG, older mice are resistant to induction of myasthenia gravis. To understand the immunological basis for this resistance, the effects of age on the B-cell responses to AChR from Torpedo californica, the inducing antigen, were addressed. As expected, the primary B-cell response was lower in 20-month-old mice than in 2-month-old mice; the isotype profile was not altered by age. When mice were re-immunized, the anti-T-AChR titers increased in both young and old animals, suggesting that a memory response was elicited. Importantly, memory B-cells activated in young animals were largely resistant to the age-associated loss of immune function and the recall memory response was vigorous. Furthermore, the antibodies produced in re-stimulated older mice were functional, as evidenced by the appearance of MG symptoms in some of these animals. Thus, by eliciting a recall memory response, the first examples of late onset MG in mice have been generated. By analogy, late onset MG in humans may be due to re-activation of B-cell responses initiated at a younger age.
D017668:Age of Onset; D000375:Aging / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002999:Clone Cells; D007132:Immunoglobulin Isotypes / Q000032:analysis; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000453:epidemiology / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology; D014101:Torpedo
D007132:Immunoglobulin Isotypes; D011950:Receptors, Cholinergic