1 / 12

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

kurt
Download Presentation

Immunoglobulin Gene Rearrangement

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related