Arrangement of genes encoding C chains. S..C..Cs Sy- TX■XE YH DH JH .M☐ H M H M H MY M G 21 S Splice Signals Intron ce signals Recombination of VH-DH-JH segments During differentiation of pluripotent stem cells,a DH segment,JH segment,and B segment,in this example DH4,JH2 and BH2,become joined.The rearranged genes are then transcribed.A second transcription follows, whereby introns re removed and mRNA is formed and translated into specific Ig H chains These gene segments obviously contribute significantly to the generation of hypervariablility in the V regions.When three segments of DNA randomly join to encode the entire H chain V region,they enhance the recombination possibilities.Thus,if there were 300 VH,12 D,and four alternative J Gene se gments and one of each becomes ociated formed (400) chains could be Recombination of VH-DH-JH segments During differentiation of pluripotent stem cells, a DH segment, JH segment, and B segment, in this example DH4, JH2 and BH2, become joined. The rearranged genes are then transcribed. A second transcription follows, whereby introns re removed and mRNA is formed and translated into specific Ig H chains. These gene segments obviously contribute significantly to the generation of hypervariablility in the V regions. When three segments of DNA randomly join to encode the entire H chain V region, they enhance the recombination possibilities. Thus, if there were 300 VH, 12 D, and four alternative J Gene segments and one of each becomes randomly associated during the differentiation, 14,400 different chains could be formed (300 x12 x 4 =14,400)