Immunoglobulin class switching

As a class change ( CSR = class switch recombination or isotype switching) is referred to in immunology one isotype switching in the B cells of the immune system. In the course of an immune response different isotypes of immunoglobulins are used on the B cells. By changing class B cells can change their antibody isotype. In the VDJ sequence of the heavy chain is changed from a C region to another, lying downstream, C region. The class change takes place especially in the germinal centers of lymph nodes.

Mechanism of class switch

At the locus for the heavy chain of immunoglobulins are constant sections for IgM ( Cμ ), IgD ( Cδ ), IgG ( C? ), IgE ( Cε ) and IgA ( Cα ). 5 ' of these genes is an intron, the so-called switch region. An exception in this case represents IgD, which has no switch region. 3 ' of these genes is the I exon (initiator -of- transcription - exon ). The Keimbahntranskripte containing the sequences from exon I, the switch region and the C region of the selected isotype start from the I exon. Transcription of the DNA Keimbahntranskripts makes accessible to the enzymes of the recombination. The open single-stranded loop is called an R -loop.

The switch regions of the isotype and the previously used for forming isotype are brought into proximity. The enzyme AID ( activation induced deaminase ) deaminated cytosine to uracil, which causes a problem in the DNA. Uracil -N- glycosylase (UNG ) from the repair mechanism BER (base excision repair ) is removed, the resulting U residues. The endonuclease Ape1 cleaves at the resulting abasic sites. The result is a double-strand break. The part of the Keimbahntranskripts, which lies between the switch regions of the isotype and the previously used region of the switch to be formed by isotype is deleted and the two strand ends to be connected to each other by non- homologous end joining.

A class-switching to an isotype whose I exon, switch region and C- region 3 'of the isotype are currently used is not possible, because this part of the DNA has been deleted.