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AID, an enzyme essential for class switching and somatic hypermutation | |
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What was known before? During the course of an immune response B cells first produce IgM and IgD, later they synthesize antibodies of different isotypes – a phenomenon called class switch. Its molecular mechanisms are the rearrangement and partial deletion of the CH locus. In the same time frame point mutations are introduced at a high rate into the rearranged variable regions of the immunoglobulin genes. This mechanism, which has been termed somatic hypermutation, enlarges the repertoire of antibody specificities and, in conjunction with selection processes, leads to the affinity maturation of antibodies. Both, class switch and somatic hypermutation coincide with oligoclonal B cell proliferation in the so-called germinal centres of the secondary lymphoid organs. The activation of B cells must, therefore, induce the expression of unknown class switch and point mutation factors. The authors hypothesized that the regulation of these factors takes place at the level of gene transcription. The important questions How can genes be identified which are differentially transcribed in resting and activated cells? Which genes are transcribed in B cells upon activation? The experiment  Related papers Sugai M, Kondo S, Shimizu A, Honjo T. 1998. Isolation of differentially expressed genes upon immunoglobulin class switching by a subtractive hybridization method using uracil DNA glycosylase. Nucleic Acids Res 26(4): 911-8. Muramatsu M, Sankaranand VS, Anant S, Sugai M, Kinoshita K, Davidson NO, Honjo T. 1999. Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells. J Biol Chem. 274(26): 18470-6. Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T. 2000. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102(5): 553-63. Related topics  B cell memory Somatic hypermutation – where does it happen? |
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