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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
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

structure of immunoglobulin
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

isotypes of immunoglobulin
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)

immunoglobulin diversity
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

rearrangement of ig gene segments
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

gene rearrangement in light chain
Gene rearrangement in light chain

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

gene rearrangement in light chain1
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

gene rearrangement in heavy chain
Gene rearrangement in heavy chain
  • Start with D-J rearrangement
  • Followed by V-DJ rearrangement

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

summary
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
references
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