1. Immunoglobulin Gene Rearrangement
Xuan Wang
01/19/2012

2. Immunoglobulin
Produced by B-cells that is used by the immune system to identify and neutralize foreign objects (antigens)
Bind to specific site on the antigens called epitope
More than 108 types
The study of antibodies began in 1890 when Kitasato Shibasaburō described antibody activity against diphtheria and tetanus toxins.

3. Structure of Immunoglobulin
2 heavy chains
2 light chains
chains are linked together by disulfide bonds
amino-terminal variable (V) region
carboxyl-terminal constant (C) region
Structure of an immunoglobulin molecule. By permission from Tizard IR, Veterinary Immunology. An Introduction, Saunders, 2001

4. Isotypes of Immunoglobulin
Light chain isotypes:
κ and λ
Heavy chain isotypes:
δ (IgD)
ε (IgE)
γ (IgG)
α (IgA)
μ (IgM)
Raul Rojas and Gerard Apodaca
Nature Reviews Molecular Cell Biology 3,   (December 2002)

5. Immunoglobulin diversity
Rearrangement of Ig gene segments
-Variable(V), Diversity(D), Joining(J)
-Multiple copies of V,D and J gene segments are tandemly arranged in the genome
-Somatic recombination and junctional imprecision result in more than 108 possibilities
Somatic hypermutation and affinity maturation
- Results in approximately one nucleotide change per variable gene, per cell division
-Increases the average antibody’s affinity for antigen

6. Rearrangement of Ig gene segments
Light-chain recombination
-consists of V and J
-recombination signal sequence(RSS)
-joining of V and J
Heavy-chain recombination
-consists of V, D and J
-RSS
-joining of D and J, followed by joining of V and DJ

7. Gene rearrangement in light chain

8. Gene rearrangement in light chain
Directed by recombination activating genes (RAG1 and RAG2)
Non-homologous end joining (NHEJ) resolves chromosome breaks to assemble a mature receptor gene (immunoglobulin or T cell receptor) and deleted extrachromosomal circle.
Ramsden DA et al. V(D)J recombination: Born to be wild. Semin Cancer Biol. 2010

9. Gene rearrangement in heavy chain
Start with D-J rearrangement
Followed by V-DJ rearrangement

10. Summary
Immunoglobulins are produced by B-cells to identify and neutralize antigens
Immunoglobulin diversity is achieved by somatic recombination, junctional imprecision and somatic hypermutation
Immunoglobulin rearrangement in light chain is created by recombination of V and J gene segments, while in heavy chain is by first joining D and J then joining V and DJ

11. Thank you!

12. References
Lodish et al. Molecular cell biology. W. H. Freeman and Company. 2008
Ramsden DA et al. V(D)J recombination: Born to be wild. Semin Cancer Biol. 2010
Raul Rojas and Gerard Apodaca. Nature Reviews Molecular Cell Biology 3,   (December 2002)
Market E et al. V(D)J recombination and the evolution of the adaptive immune system. PLoS Biol. 2003