1. Immunoglobulin Genetics

3. Light Chain Gene Families Germ line gene organization J  1 C  1 E J  2 C  2 E J  3 C  3 E J  4 C  4 E P L V  1 P L V  n P L V  2 Lambda light chain genes; n=30 P L V  1 P L V  n P L V  2 J  2 J  3 J  5 C  E J  1 J  4 Kappa light chain genes; n=300

4. Light Chain Gene Families Gene rearrangement and expression L V  1 L V  n L V  2 J  2 J  3 J  5 C  J  1 J  4 DNA P P P E P P E L V  1 L J  5 C  V  2 J  4 DNA DNA Rearrangement V C J V C Protein Transport to ER Protein Translation C L V J E L V C J RNA Transcription Primary transcript C L V J RNA Processing RNA mRNA

5. Heavy Chain Gene Family Germ line gene organization Introns separate exons coding for H chain domains Heavy chain genes; Vn=1000, Dn=15 P L V1 P L Vn P L V2 D2 D3 D1 Dn C  C  C  3 C  C  2 C  1 C  4 C  1 C  2 J2 J3 J5 J1 J4 E C H 1 H C H 2 C H 3 C H 4

6. Heavy Chain Gene Family Gene rearrangement and expression P L V1 P L Vn P L V2 D2 D3 D1 Dn C  C  J2 J3 J5 J1 J4 E DJ rearrangement P L Vn P L V1 P L V2 D2 D1 C  C  J5 J4 E DNA VDJ rearrangement D2 C  C  J5 J4 E P L V1 P L V2 DNA Transcription D2 C  C  J5 J4 E L V2 RNA Primary transcript

7. Heavy Chain Gene Family Gene rearrangement and expression E Primary transcript E J4 D2 V2 C  C  J5 L C  C  J5 L D2 J4 V2 RNA Processing A n mRNA for C  C  L D J V C  L D J V A n mRNA for C  Translation C  heavy chain C  L D J V C  L D J V C  heavy chain Transport to ER C  heavy chain V C C  D J V C  D J V C  heavy chain V C

9. Order of Ig Gene Expression + - Heavy chain gene VDJ recombination Productive rearrangement ? Yes No Transcribe/translate 1st 2nd or Apoptosis Progenitor B cell Pre B cell    (  ) Heavy chain Paternal Maternal

10. Order of Ig Gene Expression + - Light chain gene VJ recombination Productive rearrangement ? Yes No Transcribe/translate Light chain 4 th Apoptosis 1st -  2nd -  3rd -  4th -  or Pre B cell Mature B cell     + 

14. - GTCAATG - GTCAATG - + Break DNA TdT adds nucleotides Ligate N region insertion Intron J D J J J D D D Generation of N region insertions