| Themes > Science > Life Sciences > General Biology > Immunology > Recognition Systems in Immunity > Antigen Recognition: B Cells and Antibodies > Antibody diversity |
There are an estimated 109 different antibody molecules, and thus 109 distinct B cell clones in a single individual. How is this astonishing diversity generated? This problem has been resolved over the past 20 years by the demonstration that Ig genes rearrange during B cell development. The heavy chain genes has no complete exon encoding the variable region domain, instead this is split into arrays of gene segments (a diagramme of the arrangement of the human IgH segments is linked from below). Light chain genes are similarly organised on different chromosomes but they have no D gene segments. There are 51 functional VH genes and 41 Vk genes. D (diversity) and J (junctional) genes code for amino acids at the carboxyl end of V regions including CDR3. It was first noted that the organization of Ig genes in mature B cells was different from that in embryonic tissues. The pieces of genomic DNA containing antibody genes in embryonic tissue, or adult non-B cells, are larger that those from mature B cells. This implies that the DNA from mature B cells has been rearranged resulting in the excision of some DNA. It is now known that Ig genes rearrange segments with the looping out of intervening DNA. This is done in a precise order. First the heavy chain rearranges: 1) D -> J 2) V -> DJ then if a functional heavy chain (always IgM initially) results (many joins are out of frame) the light chains rearrange also in order, first kappa then if kappa is unproductive (or cannot pair with the heavy chain) lambda. 3) V -> J Expression of the first µ heavy chain prevents rearrangement on the other chromosome in a process called allelic exclusion designed to prevent expression of two antibodies by the same B cell. The same is true for the light chain. The enzymes involved in rearrangement are recombinases (lymphocyte specific), exonucleases and ligases. The recombinases recognise conserved heptamer and nonamer sequences found adjacent to the V, D and J exons. Two recombination activating genes (RAG1 and RAG2) have been shown to affect rearrangement of both genes for Ig and the T cell receptor. Click here to see a simple diagram of the mechanism of VDJ rearrangement |
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