Combinatorial Events in Generation of Antibody Diversity

Author: Nezlin R.

Source: Combinatorial Chemistry & High Throughput Screening, Volume 4, Number 5, August 2001 , pp. 377-383(7)

Publisher: Bentham Science Publishers

Abstract:

Combinatorial association of immunoglobulin gene elements is the most important process in the creation of extreme diversity of antibody molecules. The recombination of germ-line variable gene elements V, D, and J can potentially generate approximately 6000 variable genes of human heavy chains. As joining of these elements is imprecise and is occurring with nucleotide additions or deletions, the created diversity is in fact much higher. The assembled variable genes can be revised and edited resulting in a change of their affinity and even specificity. Due to somatic hypermutation, the affinity of synthesized antibody increases even more. Another variant of combinatorial recombination is joining of complete variable genes with one of the several constant genes and the formation of various immunoglobulin isotypes with different effector functions but with the same antibody specificity. Consequently, these processes not only develop the antibody repertoire but also solve some other problems of the adaptive immune response.

Keywords: immunoglobulin; hyper mutated; vd j recombination; site specific dna rearrangenment; surrogate light chains; recombination signal sequences; composite transposons; stochastic process; SOMATIC HYPERMUTATION; mismatch repair (MMR) proteins; DNA-dependent protein kinase

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1386207013330977

Publication date: 2001-08-01

• Combinatorial Chemistry & High Throughput Screening publishes full length original research articles and reviews describing various topics in combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) and/or high throughput screening (e.g. developmental, practical or theoretical). Ancillary subjects of key importance, such as robotics and informatics, will also be covered by the journal. In these respective subject areas, Combinatorial Chemistry & High Throughput Screening is intended to function as the most comprehensive and up-to-date medium available. The journal should be of value to individuals engaged in the process of drug discoveryand development, in the settings of industry, academia or government.

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