Immunoglobulin Gene
Rearrangement
Lu Tian
Deb 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 variability
2 V(D)J recombination
3 Somatic hypermutation and affinity
maturation
4 Class switching
5 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
the immunoglobulin
rearrange in a similar way
Only V and J
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>