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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 931-940 |
| Number of pages | 10 |
| Journal | Mechanisms of Ageing and Development |
| Volume | 124 |
| Issue number | 8-9 |
| DOIs | |
| State | Published - Aug 2003 |
Fingerprint
Keywords
- Autoimmunity
- B lymphocytes
- Immunological memory
ASJC Scopus subject areas
- Aging
- Biochemistry
- Developmental Biology
- Developmental Neuroscience
Cite this
Recall immune memory : A new tool for generating late onset autoimmune myasthenia gravis. / Stacy, Sue; Infante, Anthony J; Wall, Katherine A.; Krolick, Keith A; Kraig, Ellen B.
In: Mechanisms of Ageing and Development, Vol. 124, No. 8-9, 08.2003, p. 931-940.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Recall immune memory
T2 - A new tool for generating late onset autoimmune myasthenia gravis
AU - Stacy, Sue
AU - Infante, Anthony J
AU - Wall, Katherine A.
AU - Krolick, Keith A
AU - Kraig, Ellen B
PY - 2003/8
Y1 - 2003/8
N2 - 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.
AB - 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.
KW - Autoimmunity
KW - B lymphocytes
KW - Immunological memory
UR - http://www.scopus.com/inward/record.url?scp=0141629738&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0141629738&partnerID=8YFLogxK
U2 - 10.1016/S0047-6374(03)00165-9
DO - 10.1016/S0047-6374(03)00165-9
M3 - Article
C2 - 14499498
AN - SCOPUS:0141629738
VL - 124
SP - 931
EP - 940
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
SN - 0047-6374
IS - 8-9
ER -