Recall immune memory: a new tool for generating late onset autoimmune myasthenia gravis.

Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Mechanisms of Ageing and Development (Impact Factor: 3.51). 08/2003; 124(8-9):931-40. DOI: 10.1016/S0047-6374(03)00165-9
Source: PubMed

ABSTRACT 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.

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