A transposition- like mechanism can be used for other types of DNA rearrangement reactions. Such mechanism is responsible for assembly of gene fragments during development of the vertebrate immune system. Vertebrates have two specialized cells namely T- cells and B-cells that dedicated to recognize the invading organism. B cells produce antibodies that circulate in the bloodstream. T-cell produce cell surface- bound receptor protein called T-cell receptor. These classes of protein able to recognized great diverse invader molecule then starts a cascade event to destruct the invader.
Antibody diversity is generated by the rearrangement of variable region gene segments during the ...view middle of the document...
Human has 50 genes VH, 40 genes Vϰ and 40 genes Vλ (Albert et al., 2002).
Combinatorial joining of gene segments magnifies antibody diversity by random rearrangement of VJ and VDJ in somatic cells. 40 Vϰ and 5 Jϰ genes able to form 200ϰ chain combinations. 40 Vλ and 4 Jλ genes able to form 160λ chain combinations. 50 VH , 20 D and 6 JH genes approximately form 6,000 H chain combinations.
Junctional diversification during gene segment joining is the imprecise joining and random insertion. The recombination between V-J and V-D-J is not always perfect and if errors occur during recombination event, additional diversity occurs. The diversity generated by this mechanism is occurring in the third hypervariable region thus directly affecting combining site of the antibody. After the hairpin loop is opened, thr free DNA ends can be trimmed cause the loss of nucleotides from the free end. Pier, Lyczak and Wetzler (2004) believe that exonuclease activity is involved. Exonuclease activity is not only removed P-nucleotides that already added to gene but also nucleotides that were originally part of the immunoglobulin gene. Junctional diversity also has the potential to alter the reading frame of exon.
Any B cell has potential of combinatorial joining of possible light and heavy chains before transcribed. Thus dissimilar combinations of light and heavy chains within individual B cells add further diversity. Pier et al. (2004) stated that in human, the amount of potential diversity calculated is as follow.
H chain diversity: 38 to 46 IGHV genes, 23 to 27 IGHD genes and 6 IGHJ genes able to produce 5244 to 7452 possible H-chain variable-region combinations.
L-chain diversity: 30 to 44 IGKV genes, 5 IGKJ genes or 150 to 220 possible ϰ L-chain variable regions, 29 to 33 IGLV genes and 4 to 5 IGLJ genes, or 116 to l65 possible λ L-chain variable regions.
However, the total possible diversity is; low end, (5244 x 150) + (5244 x 116) = 1.39 x 106 HL combination while at high end, (7452 x 220) + (7452 x 165) = 2.87 x 106 HL combinations.
Somatic hypermutation (SHM) happen particularly in the place that codes for the second hypervariable region is within the V-region. The point mutation happens during secondary immune response. The individual nucleotides in VJ or VDJ units are replaced with alternative bases thus most likely altering the specificity of the encoded Ig (Generation of Ab Diversity, n.d.). According to Teng and Papavasiliou (2007) initiation of hypermutation process is by activation-induced cytidine deaminase (AID) converts cytidine to uridine. When the two DNA strands of the immunoglobulin gene become temporarily...