Class change
In immunology, a class change (CSR = class switch recombination or isotype switching ) is an isotype change in the B cells of the immune system. In the course of an immune response, different isotypes of the immunoglobulins are needed on the B cells. By changing classes, B cells can change their antibody isotype. In the VDJ sequence of the heavy chain, there is a switch from one C region to another, downstream, C region. The class change takes place mainly in the germinal centers of the lymph nodes .
Mechanism of class change
At the gene locus for the heavy chain of immunoglobulins there are constant segments for IgM (Cμ), IgD (Cδ), IgG (Cγ), IgE (Cε) and IgA (Cα). At the 5 'end of these genes there is an intron , the so-called switch region. IgD, which does not have a switch region, is an exception. The I exon (initiator-of-transcription exon) is located at the 3 'end of these genes. The germline transcripts, which contain the sequences from the I exon, the switch region and the C region of the selected isotype, start from the I exon. The transcription of the germline transcript makes the DNA accessible to the enzymes of recombination. The open single strand loop is referred to as the R loop .
The switch regions of the isotype used so far and the isotype to be formed are brought into proximity. The enzyme AID (activation induced deaminase) deaminase cytidine to uracil, which is a disruptive factor in the DNA. Uracil-N-glycosylase (UNG) from the repair mechanism BER (base excision repair) removes the U residues. The endonuclease Ape1 cuts at the abasic sites that have formed. A double strand break occurs. The part of the germline transcript which lies between the switch regions of the isotype used so far and the switch region of the isotype to be formed is deleted and the two strand ends are connected to one another by non-homologous end joining .
A class change to an isotype whose I exon, switch region and C region are 3 'of the isotype currently used is not possible, since this part of the DNA has already been deleted.