preview

Class Twitch Recombination Essay

Decent Essays
Open Document

Somatic hypermutations and Class Switch Recombination.
When B cells have successfully rearranged their IgH and IgL loci and express a BCR they will leave the bone marrow as immature B cells and become transitional B cells that migrate to secondary lymphoid tissues. In the lymphoid tissues B cells may be exposed to antigen and the initial antigen encounter will initiate a dynamic cascade of cell signalling events that ultimately promotes cellular activation and proliferation57-60. In the secondary lymphoid organs this area of B cell expansion is a visible structure and termed the germinal centre (GC)61. As B cells divide, their receptor undergoes somatic hypermutation (SHM); a mechanism whereby the IgH and IgL genes are hypermutated and fine …show more content…

SHM occurs by two mechanisms: 1) DNA replication reads the uracil as a thymidine and pairs it with an adenine which results in a C to T or G to A transition. This type of mutation only requires AID activity68, 69. 2) Uracil is a pyrimidine normally found in RNA and the base-excision repair system will therefore attempt to correct the mistake by removing the uracil. This creates an abasic site in the DNA strand. The removal of the uracil is executed by an enzyme called uracil N-glycosylase (UNG)70, 71. In the abasic site a random nucleotide may be inserted leading to both transitions (G:C into A:T) and transversions (G:C into C:G)68. Ultimately, for both mechanisms it is the misreading of a low fidelity polymerase that is responsible for the introduction of the point mutation72, 73. AID only binds single stranded (ss) DNA and thus only functions on actively transcribed alleles where transcription temporarily separates of the two DNA strands within the transcription bubble74-76. Sequencing studies support this in that mutations only occur downstream of the VH-gene promoter suggesting the importance of this promoter for AID activity. It is hypothesized that AID is recruited

Get Access