immunoglobulin gene rearrangement

18
Immunoglobulin Gene Rearrangement Lu Tian Deb Walter

Upload: jalene

Post on 22-Feb-2016

86 views

Category:

Documents


0 download

DESCRIPTION

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). - PowerPoint PPT Presentation

TRANSCRIPT

Page 1: Immunoglobulin Gene Rearrangement

Immunoglobulin Gene Rearrangement

Lu TianDeb Walter

Page 2: Immunoglobulin Gene Rearrangement

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

Page 3: Immunoglobulin Gene Rearrangement

Isotypes

IgA IgD IgE IgG IgM

http://en.wikipedia.org/wiki/File:Mono-und-Polymere.svg

Page 4: Immunoglobulin Gene Rearrangement

Structure of Immunoglobulin

http://www.ebioscience.com/knowledge-center/antigen/immunoglobulin/structure.htm

Page 5: Immunoglobulin Gene Rearrangement

Immunoglobulin diversity

1 Domain variability2 V(D)J recombination3 Somatic hypermutation and affinity maturation4 Class switching5 Affinity designations

Page 6: Immunoglobulin Gene Rearrangement

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 .

Page 7: Immunoglobulin Gene Rearrangement

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

Page 8: Immunoglobulin Gene Rearrangement

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

Page 9: Immunoglobulin Gene Rearrangement

Germline Immunoglobulin DNA

Jung et al., Annual review of immunology 24 (2006)

Page 10: Immunoglobulin Gene Rearrangement

V(D)J Recombination and 12/23 Rule

Tonegawa, T. Nature 302,5909 (1983)

Page 11: Immunoglobulin Gene Rearrangement

RAG Mediated DNA Rearrangements

Bassing et al. Cell 109 (2002)

Page 12: Immunoglobulin Gene Rearrangement

Hairpin Opening and Artemis Protein

Ma et al. Cell Press 108 (2002)

Page 13: Immunoglobulin Gene Rearrangement

V(D)J Joining

Murphy, Geha and Notarangelo. Immuno Biology 8th edition (2011)

Page 14: Immunoglobulin Gene Rearrangement

Review of V(D)J Joining

Bassing et al. Cell 109 (2002)

Page 15: Immunoglobulin Gene Rearrangement

Regulation of Further Recombination

Jung et al., Annual review of immunology 24 (2006)

Page 16: Immunoglobulin Gene Rearrangement

Somatic Hypermutation

Jacobs and Bross. Curent opinion in immunology. 13 (2001)

Page 17: Immunoglobulin Gene Rearrangement

Class Switch Recombination

Manis et al. Trends in immunology. 23, 1 (2002)

Page 18: Immunoglobulin Gene Rearrangement

Severe Combined Immunodeficiency (SCID) Mice

Jackson Laboratories <jax.org>