Immunoglobulin Gene Rearrangement

Xuan Wang01/19/2012

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.

http://aplasticcentral.com/Aplastic_Facts/Aplastic_Immune_System.htm#Antibodies

Structure of Immunoglobulin

Structure of an immunoglobulin molecule. By permission from Tizard IR, Veterinary Immunology. An Introduction,

Saunders, 2001

• 2 heavy chains• 2 light chains• chains are linked together

by disulfide bonds• amino-terminal variable

(V) region• carboxyl-terminal constant

(C) region

Isotypes of Immunoglobulin

Raul Rojas and Gerard ApodacaNature Reviews Molecular Cell Biology 3, 944-956 (December 2002)

• Light chain isotypes:κ and λ

• Heavy chain isotypes:δ (IgD)ε (IgE)γ (IgG)α (IgA)μ (IgM)

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

• 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

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

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

• Start with D-J rearrangement

• Followed by V-DJ rearrangement

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

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

Thank you!

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, 944-956 (December 2002)

• Market E et al. V(D)J recombination and the evolution of the adaptive immune system. PLoS Biol. 2003