Immunoglobulin Gene Rearrangement
description
Transcript of Immunoglobulin Gene Rearrangement
Immunoglobulin Gene Rearrangement
Lu TianDeb Walter
Immunoglobulin
• A Y-shaped protein produced by B cells that is used by the immune system to identify and neutralize foreign objects (bacteria and viruses).
• Each antibody contains a paratope that is specific for one particular epitope on an antigen, allowing these two structures to bind together.
http://en.wikipedia.org/wiki/Antibody
Isotypes
IgA IgD IgE IgG IgM
http://en.wikipedia.org/wiki/File:Mono-und-Polymere.svg
Structure of Immunoglobulin
http://www.ebioscience.com/knowledge-center/antigen/immunoglobulin/structure.htm
Immunoglobulin diversity
1 Domain variability2 V(D)J recombination3 Somatic hypermutation and affinity maturation4 Class switching5 Affinity designations
Immunoglobulin Gene Rearrangements
• The ability of cells of the immune system to make antibodies requires multiple programmed rearrangements of immunoglobulin genes.
• Randomly combines Variable, Diverse, and Joining gene segments in vertebrate lymphocytes.
• Because of its randomness in choosing different genes, is able to diversely encode proteins to match antigens .
Rearrangement in Heavy Chain
V, D, J
First, D-J recombination
followed by the joining of V gene segment, forming a rearranged VDJ gene segment.
Any DNA between these gene segments is deleted
http://en.wikipedia.org/wiki/V(D)J_recombination
Rearrangement in Light Chain
Two types of chains:The kappa (κ) and lambda (λ) chains, but
Only V and J
the immunoglobulin rearrange in a similar way
http://pathmicro.med.sc.edu/mayer/gen-2.jpg
Germline Immunoglobulin DNA
Jung et al., Annual review of immunology 24 (2006)
V(D)J Recombination and 12/23 Rule
Tonegawa, T. Nature 302,5909 (1983)
RAG Mediated DNA Rearrangements
Bassing et al. Cell 109 (2002)
Hairpin Opening and Artemis Protein
Ma et al. Cell Press 108 (2002)
V(D)J Joining
Murphy, Geha and Notarangelo. Immuno Biology 8th edition (2011)
Review of V(D)J Joining
Bassing et al. Cell 109 (2002)
Regulation of Further Recombination
Jung et al., Annual review of immunology 24 (2006)
Somatic Hypermutation
Jacobs and Bross. Curent opinion in immunology. 13 (2001)
Class Switch Recombination
Manis et al. Trends in immunology. 23, 1 (2002)
Severe Combined Immunodeficiency (SCID) Mice
Jackson Laboratories <jax.org>