Transcript Immunoglobulin Gene Rearrangement

Immunoglobulin Gene
Rearrangement
Xuan Wang
01/19/2012
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
• 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
• 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
• 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%2
C+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