Switch circular DNA formed in cytokine-treated mouse splenocytes: Evidence for intramolecular DNA deletion in immunoglobulin class switching

Matsuoka, Masao; Yoshida, Kazuya; Maeda, Takeshi; Usuda, S; Sakano, Hitoshi

doi:10.1016/0092-8674(90)90247-c

Cited by 228 publications

(120 citation statements)

References 34 publications

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“…The evidence for DNA breaks in class-switch recombination is clear since the process involves the excision of intervening DNA between the upstream and downstream isotypes with the excised DNA detectable in the form of switch circles (Iwasato et al 1990;Matsuoka et al 1990;Von Schwedler et al 1990). The resolution of these breaks, necessary for the successful completion of switching, is dependent upon components of the DNA-dependent protein kinase (Casellas et al 1998;Manis et al 1998;Rolink et al 1996).…”

Section: Dna Breaks In Hypermutation and Isotype Switchingmentioning

confidence: 99%

In vivoandin vitrostudies of immunoglobulin gene somatic hypermutation

Sale

Bemark

Williams

et al. 2001

Phil. Trans. R. Soc. Lond. B

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Following antigen encounter, two distinct processes modify immunoglobulin genes. The variable region is diversi¢ed by somatic hypermutation while the constant region may be changed by class-switch recombination. Although both genetic events can occur concurrently within germinal centre B cells, there are examples of each occurring independently of the other. Here we compare the contributions of classswitch recombination and somatic hypermutation to the diversi¢cation of the serum immunoglobulin repertoire and review evidence that suggests that, despite clear di¡erences, the two processes may share some aspects of their mechanism in common.

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Section: Dna Breaks In Hypermutation and Isotype Switchingmentioning

confidence: 99%

In vivoandin vitrostudies of immunoglobulin gene somatic hypermutation

Sale

Bemark

Williams

et al. 2001

Phil. Trans. R. Soc. Lond. B

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“…By means of CSR, the C m heavy chain of Ig is replaced by a different C x heavy chain, thus allowing the production of immunoglobulins of various isotypes with the same antigen affinity since the V region is left unchanged [Iwasato et al, 1990;Kinoshita and Honjo, 2000;Matsuoka et al, 1990]. Conversely, the SHM process modifies the antigen affinity (but not the isotype) of an antibody by introducing mutations in the V region at a very high frequency (1 Â 10 -3 bases per generation) [Jacobs et al, 2001;Storb et al, 1998].…”

Section: Introductionmentioning

confidence: 99%

Activation-induced cytidine deaminase: structure–function relationship as based on the study of mutants

et al. 2006

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For the Immunogenetics Special IssueActivation-induced cytidine deaminase (AID; gene symbol AICDA) is the key molecule required to induce immunoglobulin (Ig) class switch recombination (CSR) and somatic hypermutation (SHM) of the variable regions of Ig genes. Its deficiency causes a form of hyper-IgM (HIGM) syndrome. The study of natural AID mutants associated with HIGM as well as engineered mutants led to the characterization of the active domains of the protein. AID, through its cytidine deaminase activity, induces a targeted DNA lesion as an early step required for both CSR and SHM. Besides its cytidine deaminase activity, AID plays a further essential role in CSR, likely by recruiting CSR-specific cofactors by its C-terminus. A similar binding of SHM-specific cofactors to the N-terminal part is suggested by the functional characteristics of N ter AID artificial mutants. These data require confirmation in vivo. Finally, AID acts as a homo-, di-, or multimeric complex. Together, these data strongly suggest that AID, a master molecule for antibody diversification, exerts its activity on CSR not only as a cytidine deaminase enzyme but also as a docking protein, recruiting specific cofactors to a multimeric complex.

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“…Because AID deficiency did not affect either GLT synthesis or nonhomologous end-joining repair, AID is most likely to be involved in a critical step of CSR. CSR is accompanied by looping-out deletion of a DNA segment containing C and other C H genes from the chromosome (13)(14)(15). A resultant circular DNA (CD) can be a good marker for active CSR if it decays rapidly.…”

mentioning

confidence: 99%

A hallmark of active class switch recombination: Transcripts directed by I promoters on looped-out circular DNAs

Kinoshita

Harigai

Fagarasan

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

157

155

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To specify when and where Ig class switch recombination (CSR) takes place, a good molecular marker closely associated with active CSR is required. CSR is accompanied by deletion of circular DNA from the Ig heavy chain locus. The circular DNA contains a DNA segment between S and a target S region including its I promoter, which is driven by specific cytokine stimulation before CSR. We found that the specific I promoter is still active in looped-out circular DNA and directs production of I-C transcripts termed "circle transcripts.

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Switch circular DNA formed in cytokine-treated mouse splenocytes: Evidence for intramolecular DNA deletion in immunoglobulin class switching

Cited by 228 publications

References 34 publications

In vivoandin vitrostudies of immunoglobulin gene somatic hypermutation

In vivoandin vitrostudies of immunoglobulin gene somatic hypermutation

Activation-induced cytidine deaminase: structure–function relationship as based on the study of mutants

A hallmark of active class switch recombination: Transcripts directed by I promoters on looped-out circular DNAs

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