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Immunoglobulin Gene Rearrangement

Immunoglobulin Gene Rearrangement. Xuan Wang 01/19/2012. Immunoglobulin. P roduced 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 10 8 types

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Immunoglobulin Gene Rearrangement

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  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 KitasatoShibasaburō described antibody activity against diphtheriaandtetanus toxins. http://aplasticcentral.com/Aplastic_Facts/Aplastic_Immune_System.htm#Antibodies

  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, 944-956 (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 http://flipper.diff.org/app/items/info/1052

  7. Gene rearrangement in light chain http://www.lookfordiagnosis.com/mesh_info.php?term=Gene+Rearrangement%2C+B-Lymphocyte%2C+Light+Chain&lang=1

  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 http://en.wikipedia.org/wiki/V(D)J_recombination

  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 • Lodishet 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, 944-956 (December 2002) • Market E et al. V(D)J recombination and the evolution of the adaptive immune system. PLoS Biol. 2003

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