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>