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Antibody Diversity-Gene
Rearrangement
www.creative-biolabs.com
• Variable Domains
• Antigen-binding
• Activity
• Constant Domains
• Functional
• Activities
Antibody Structure and Function
What is Antibody Diversity ? Source of Antibody Diversity
• Millions of antigens
• Produce specific antibody against all antigens
• Diversification
•One gene for each protein.
•There are around 40000 genes in our genome.
But our immune system apparently produce antibody in the order of 1010
• Antibody Gene Rearrangement
• Junctional Diversity
• Antibody Isotype Switching
Problem ?
Antibody Diversity-Gene Rearrangement
Source of antibody
diversity
• Somatic Hypermutation
• Affinity Maturation
Hematopoietic stem cell
Lymphoid cell
Pro-B cell
Pre-B cell
Partial heavy-chain gene rearrangment
Complete heavy-chain gene rearrangment
Immature B cell
Light-chain gene rearrangment
Mature B cell
Change in RNA processing
CELL Ig EXPRESSED
None
None
None
μ Heavy chain
+surrogate light chain
mIgM
mIgM + mIgD
B Lymphocyte Development (1)
Bone marrow
B Lymphocyte Development ( 2 )
Mature B cell
Differentiation
IgM-secreting plasma cells
Class switching
Memory B
cells of various
isotypes
Antigen stimulation
IgM
Plasma cells
secreting various
isotype
IgG IgA IgE
mIgM + mIgD
Peripheral lymphoid organs
Activated B cell
Organization of lg Genes
Somatic recombination
Polypeptide chain
Transcription
Somatic recombination
Germline DNA
D-J rearranged
DNA joined
Splicing
Translation
DNARNAProtein
Light chain Heavy chain
Antibody Gene Rearrangement
Heavy Chain Locus and VDJ Rearrangement
Kappa Light Chain Rearrangement
Recombination Signal Sequences (RSSs)
V(D)J recombinase = RAG1 and RAG2
Looping out of DNA
during rearrangement
Mechanism of Variable-Region DNA Rearrangements
• Between V, D, and J segments
• Signal for recombination
• 2 kinds
• 12 base pairs (bp) – 1 turn of DNA
• 23 bp – 2 turns of DNA
• 12 can only join to 23 and vice versa
• Monoclonal antibodies
A New World of Possibilities
• Engineering mice with human
immune systems
• Generating chimeric and
hybrid antibodies for clinical
use
• Antibody library: construct
more effective Ab for target
Antibody Sequencing Service by Creative Biolabs
• 100% accuracy
• For different
isotypes
• Within 10 days • For Various types
of antibody
CONTACT US
45-1 Ramsey Road, Shirley, NY 11967, USA
Tel: 1-631-871-5806 Fax: 1-631-207-8356
Email: info@creative-biolabs.com
Web: www.creative-biolabs.com

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Antibody Diversity-Gene Rearrangement

  • 2. • Variable Domains • Antigen-binding • Activity • Constant Domains • Functional • Activities Antibody Structure and Function
  • 3. What is Antibody Diversity ? Source of Antibody Diversity • Millions of antigens • Produce specific antibody against all antigens • Diversification •One gene for each protein. •There are around 40000 genes in our genome. But our immune system apparently produce antibody in the order of 1010 • Antibody Gene Rearrangement • Junctional Diversity • Antibody Isotype Switching Problem ? Antibody Diversity-Gene Rearrangement Source of antibody diversity • Somatic Hypermutation • Affinity Maturation
  • 4. Hematopoietic stem cell Lymphoid cell Pro-B cell Pre-B cell Partial heavy-chain gene rearrangment Complete heavy-chain gene rearrangment Immature B cell Light-chain gene rearrangment Mature B cell Change in RNA processing CELL Ig EXPRESSED None None None μ Heavy chain +surrogate light chain mIgM mIgM + mIgD B Lymphocyte Development (1) Bone marrow
  • 5. B Lymphocyte Development ( 2 ) Mature B cell Differentiation IgM-secreting plasma cells Class switching Memory B cells of various isotypes Antigen stimulation IgM Plasma cells secreting various isotype IgG IgA IgE mIgM + mIgD Peripheral lymphoid organs Activated B cell
  • 7. Somatic recombination Polypeptide chain Transcription Somatic recombination Germline DNA D-J rearranged DNA joined Splicing Translation DNARNAProtein Light chain Heavy chain Antibody Gene Rearrangement
  • 8. Heavy Chain Locus and VDJ Rearrangement
  • 9. Kappa Light Chain Rearrangement
  • 10. Recombination Signal Sequences (RSSs) V(D)J recombinase = RAG1 and RAG2 Looping out of DNA during rearrangement Mechanism of Variable-Region DNA Rearrangements • Between V, D, and J segments • Signal for recombination • 2 kinds • 12 base pairs (bp) – 1 turn of DNA • 23 bp – 2 turns of DNA • 12 can only join to 23 and vice versa
  • 11. • Monoclonal antibodies A New World of Possibilities • Engineering mice with human immune systems • Generating chimeric and hybrid antibodies for clinical use • Antibody library: construct more effective Ab for target
  • 12. Antibody Sequencing Service by Creative Biolabs • 100% accuracy • For different isotypes • Within 10 days • For Various types of antibody
  • 13. CONTACT US 45-1 Ramsey Road, Shirley, NY 11967, USA Tel: 1-631-871-5806 Fax: 1-631-207-8356 Email: info@creative-biolabs.com Web: www.creative-biolabs.com