Immunoglobulin gene recombination and RAG enzymes

Enter text here

1. Lymphocytes

   • Highly diverse antigen receptors (immune repertoire)
   • Diversity achieved by rearrangement of genes coding for BCR

2. Variable and constant regions

   • Heavy chain: variable region comprised of protein segments encoded by variable, diversity and joining genes
   • Light chain: variable region comprised of variable and joining gene products

3. Recombination is driven by RAG up regulation

   • Recombination of Ig genes is controlled by recombination-activating genes: RAG-1 RAG-2
   • RAG enzymes catalyze the formation of stem and loop structures in the Ig DNA that brings together distant exons
   • Enzymes cleave off the loop and gap the DNA is filled in nucleotides under direction of terminal deoxyribonucleotidyl transferase
   • Random nucleotides can be added that are not encoded by germline DNA but contribute further to diversity of Ig
   • Steps in recombination
     • Synapsis: portions of the chromosome made available for recombination
     • Cleavage: double strand breaks generated
     • End processing: addition or removal of bases results in greater diversity generation
     • Joining: coding ends are brought together and ligated

4. Central tolerance

   • Immature B cells in bone marrow express IgM
   • Cells with BCR that bind self antigens with high affinity can be
     • deleted by induction of apoptosis (clonal deletion)
     • induced to enter state of anergy
     • replace the light chain (receptor editing)