Figure 4. Translocon and cluster genome organization of the antibody genes.

The translocon organization (top) of the gene segments as it occurs in camelids to produce the H-chain of classical antibodies and the H-chain of HCAbs. For the former antibody type, one member of the different VH families (shown VH4 and VH3) are rearranged with one of the D and one of the J genes to be transcribed with Cµ and after a class switch with the Cγ1, Cε, or Cα. Note that the greater the number of families and the more members per family, the larger the repertoire will be. For the production of HCAbs, one of the VHH3 genes (or the VH4) has to be rearranged with one of the D and one of the J genes of the same translocon before transcription occurs with the Cµ, and after a class switch, with the Cγ2 (or Cγ3 not shown). To generate the H chain of an H₂L₂ antibody, a VH3 gene (or VH4) has to recombine with one D and one J minigene and should be transcribed with the Cµ, or after a class switch with any other C isotype except Cγ2 or Cγ3. Cartilaginous fish have a cluster organization of their antibody genes whereby each cluster contains a dedicated V element followed by two or three D genes and a J gene. After rearrangement of these minigenes, cotranscription occurs with the W constant gene or with the C-NAR genes to produce classical H₂L₂ antibodies or HCAbs, respectively. There are multiple clusters in the genome of shark and the V minigenes of some clusters belong to either type I, type II (both clustered with 3-D segments), or type III (clustered with 2-D segments) minigenes.