Lymphocyte Selection and Tolerance Chander Raman 2004. Lecture Focus: Lymphocyte Selection: Central Tolerance T-cell selection B-cell selection Peripheral Tolerance Peripheral control of autoreactivity. Breakdown of tolerance Autoimmune diseases Restoration of tolerance
Clonal deletion occurs by induction of programmed cell death or apoptosis
(Positive selection for ability to recognize antigen)
Death by Neglect
(Positive selection based on MHC reactivity)
Autoantibodies to different organs shown in GREEN in AIRE-deficient mice
AIRE allows for the expression of antigens to which T-cells are negatively selected.
B-Cell Development are negatively selected.
Sensitive to Negative Selection – Central Tolerance
B-Cell Selection in the Bone Marrow are negatively selected.
Binding to self molecules in the bone marrow can lead to the deletion or inactivation of immature B cells.
Survival are negatively selected.
Control of autoreactive T cells in the periphery is termedPeripheral Tolerance
Anergy are negatively selected.
Maloy and Powrie, Nature Immunol. 2:816
Feinberg & Silvestri, Nature Immunol, 3:215
Lutz and Schuler, Trends Immunol: 23:9
Immunity vs Tolerance in Peripheral B Cells are negatively selected.
Focus on Autoimmunity
Nature Immunology, Sept 2001 (Vol 2)
Development of Autoimmunity Disease
Systemic Lupus Erythematosus Disease
Contribution of Susceptibility Gene Alleles to Development of Autoimmunity
Therapeutic Intervention of Autoimmunity
Ware, Nature. 404:949