Title: Antigen Receptor Genes and Antibody Diversity
1Antigen Receptor Genes and Antibody Diversity
2Overview of B Cell Development,
Activation, Antibody Production
3The expression of antigen receptor genes is the
Key event in lymphocyte Development/Maturation
- Functional Ag. Receptor Created in Immature
Lymphocytes - B Cells Bone Marrow
- T Cells Thymus
4The expression of antigen receptor genes is the
Key event in lymphocyte development/maturation
- Required for
- Generation of Diverse Repertoire
- Selection Against lymphocytes that are Self
Reactive-NEGATIVE SELECTION - Selection for Lymphocytes With Useful
Specificities-POSITIVE SELECTION
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6Formation of Functional Antigen Receptor Genes in
Lymphocytes
7Overview of B Cell Development,
Activation, Antibody Production
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10Heavy Chain
- Variable Region
- Region Encoded for by 3 separate gene segments
- VH (Variable)
- DH (Diversity)
- JH (Joining)
- Constant Region
- C Gene Segments
11Light Chain
- Variable Region
- Encoded for by 2 separate gene segments
- VL (Variable)
- JL (Joining)
- Constant Region
- C (CL) Gene Segment
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13Complete Variable Regions are Generated by the
Somatic Recombination of Separate Gene
Fragments-Gene Rearrangement
14Gene Rearrangement
- Occurs in Bone Marrow
- Antigen-Independent
- Before Antigenic Exposure.
15How to code for different antibodies?
- A few groups of gene segments, combining 1 gene
segment from each group to form a complete Ab
16Recombination and Expression of Ig Genes
17Recombination and Expression of Ig Genes(Contd.)
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19Gene Rearrangement(Heavy chain)
- In the course of differentiation, a B cell
rearranges its DNA so as to join one VH gene
segment to one DH segment and one JH segment.
The joined VDJ unit codes for the entire variable
region of the heavy chain. - Mediated by Recombinases
- Recombination Signal Sequence (RSS)
20Antibody Diversity
- Combinatorial Diversity (V-D-J joining)
- Combinatorial association of heavy and light
chains - Junctional Diversity
- Somatic Hypermutation
21Combinatorial Diversity
- The ability to create many different
specificities by making many different
combinations of a small number of gene segments.
(2005)(1006)(200126)
22Combinatorial Diversity
2.3 X 107
Specific antibody
14,400
VH
VL
1600
V 200
D 12
J 6
?
600
?
1000
V 200
J 5
V 100
J 6
23Junctional Diversity
Joining of V and the J, or V, D and J segments To
form CODING JOINT is Imprecise Addition and
Deletion of Nucleotides Diversity of the
Hypervariable region 3 (CDR3)
24Mechanisms of Diversity in Antigen Receptors
25Deletions
26Additions
Terminal deoxyribonuceotidyl transferase (TdT)
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28Allelic Exclusion
Monospecificity Of B Cells