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5 Cards in this Set
- Front
- Back
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Receptor Editing Rescues some Self-Reactive B-Cells
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Strong ligation of IgM by self antigen
>>Arrest of B-cell development and continued light chain rearrangements: Low cell-surface IgM >>A new receptor specificity is now expressed: 1. If the new receptor is still self-reactive, the B-cell undergoes apoptosis 2. If the new receptor is no longer self-reactive, the immature B-cell migrates to the periphery and matures |
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Binding of self molecules in bone marrow leads to death or inactivation of immature B-Cells
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Immature B-Cells in Bone Marrow:
1. Multivalent self-molecule >>clonal deletion or receptor editing leading to apoptosis 2. Soluble self-molecule >>migrates to periphery >>leads to anergic B-cell 3. Low affinity noncross-linking self molecule >>migrates to periphery >>leads to mature B-cells that are clonally ignorant 4. No self reaction >>migrates to periphery >>leading to maturation of B-cell |
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Proposed Population Dynamics of Conventional (B2) B-Cells
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In Bone Marrow
--open repertoire of mature B-cells. Tolerance induction In Blood and secondary lymphoid tissues --additional tolerance induction. Self tolerant immature B-cells and anergized B-cells, leading to: 1. No Positive selection: B cells fail to enter lymphoid follicles >>B-cells have half life of about about 3 days 2. Positive Selection: B cells successfully enter lymphoid follicles >>Long-lived mature recirculating naive B-cells (half-life about 3-6wks) 3. Stimulation by antigen >>long-lived mature recirculating memory B-cells. >>express high affinity IgA, IgE, IgG |
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Positive Selection during B-Cell Development is Reflected by Recruitment into Different B-Cell Subsets
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Immature B-Cell >> Mature B-Cell
1. B1 cells 2. Marginal Zone B Cells 3. B2 cells 4. Memory B Cells * Positive selection is NOT mediated by antigen but is determined by a host of factors such as binding affinity to stromal cells in 2' lymphoid tissues and signal transduction capability |
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B Cell Development
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1. Gene segment recombination
2. Negative Selection: --selection against self-reactive cells 3. Positive Selection --selection for cells in 2' lymphoid tissues |
