Immunoglobulin Diversity

Immunoglobulin Diversity is capable of eliciting an antibody response in most cases. Each having different antibody molecules of many different specificities slightly and the strength of antigen binding affinity or unique, as well as a variety, further one antigenic determinant, even response to the antigen. The total number of available features of the individual antibodies is known as the repertoire of the immunoglobulin or antibody repertoire, it is possible in at least 1011, is far in humans. However, it is intended that the invention not be limited by the total number of B cells in an individual, the number of specific antibodies present at any time, and is connected to individual antigens.

It before it was possible to examine the immunoglobulin genes directly, two hypotheses about the origin of these differences are present. Reproductive theory, the different strands of immunoglobulins and antibody repertoire is assumed that there is a single gene that is highly genetic. On the other hand, somatic diversification theory, during the life of the individual repertoires observed was proposed to be generated by a limited number of genetic V region sequences that undergo changes in B-cells. The antibody repertoire, in fact, cloning immunoglobulin genes are shown to be produced by DNA rearrangement during the development of B cells. As can be seen in this part of the head, DNA sequences encoding the V regions are attached to each locus by selecting from a relatively small group of gene segments inherited. Diversity is enhanced by the process of somatic hypermutation in mature activated cells. The concept of multiple genes of embryonic germ theory embodied, proof of true diversification theory of somatic cells, is essentially correct in this way.

non-lymphoid cells, but mature B lymphocytes is a considerable distance from some sequence encoding the region C, gene segment encoding the majority of the V region of an immunoglobulin chain, V-region sequences and n is , as a result of gene rearrangement, assembled is very close to the area C. Reorganization of the immunoglobulin genes when it became possible it with a restriction enzyme analysis of the first, consider the organization of the immunoglobulin genes in both non-lymphoid cells and B cells by Southern blotting , initially, I was discovered 25 years ago. In this step, chromosomal DNA was identified by hybridization with radiolabeled DNA probes specific for the DNA sequence is cleaved with the first restriction enzyme and the corresponding DNA fragments containing the C-region sequences and V-particularly . Is a germline DNA from non-lymphoid cells in the C-region sequences and V-determined from a sample of DNA fragments. However, the DNA of the antibody-producing B cells, the C-region sequences and V-, these indicate that the DNA rearrangement has occurred, the same DNA fragment on. Typical experiment with human DNA will be displayed in.

V region of the immunoglobulin heavy or light chain is encoded by a gene segment or a plurality of region V,. Light chain V regions for are encoded by DNA segments of the two separate. The first segment encoding the amino acids 95-101 of the first of the light chain, the V gene segment, V. second segment, the remaining portion of domain V (up to 13 amino acids) is called the code a large part of the domain The encoding, it is called a J gene segments or multiplexing.

Create an exon rearrangement leading to production of a complete immunoglobulin heavy chain gene, encoding the light chain V region of the whole shown in inches of bonding J gene segments and V, and not interrupted. The J gene segment, which is located far from the relatively area C, however, is located in the adjacent area C, and consolidated segment, V gene segment, J is close to the C-region sequences and V gene segments in unrearranged DNA I’m carrying the V gene. Gene rearrangement of V region, J segment is separated from the sequence of the C-region of the intron. In the experiment shown in germline DNA fragment identified by “V region probe” contains specific “C-field probe” and V gene segments, comprises a sequence of C region gene, and J segments actually You. I make the RNA of complete immunoglobulin light chain V region exons that binds the C-region sequences of splicing RNA transcription.

For simplicity as if there was no only one copy of each gene segment, so far, we have discussed the formation of a complete immunoglobulin V region sequences. In fact, multiple copies of the gene segments of all the germ cell DNA exists in. To assemble a V region to make the diversity of V region of an immunoglobulin, which is a random selection of the gene segments of one of each type. Gene segments of all decision not shown login using cloning and sequencing of the gene, as in the number of functional gene segment of each type in the human genome, it is not possible to encode a protein that they work There is no functional units accumulated mutations. Is referred to as a “false” They, because there in the DNA of the germ cells of many V and J gene segment D, and none of them is not necessary. This reduces the pressure on the gene of the development of any remains of the lead of a relatively large number of false segment intact. It is possible to undergo rearrangement as a functional gene segments Usually only a part of the pseudogene thereof, a substantial portion of the dislocation comprises a pseudo-gene, thus non-functional.