In B cells, there is the capacity to switch isotype through a class-switch recom
ID: 211038 • Letter: I
Question
In B cells, there is the capacity to switch isotype through a class-switch recombination (CSR).
a. What are the first classes of immunoglobulin heavy chains produced from the promoter for VDJ in naïve B cells?
b. In the course of an immune response, the B cell can then produce IgG3, IgG1, IgG2b, IgG2a, IgE, and IgA. What type of genomic rearrangement occurs in class switching? Describe what features in the genome are required for CSR and briefly how DNA breaks are generated to mediate the recombination. Are specific sequences required?
Explanation / Answer
a. The first classes of immunoglobulin heavy chains produced from the promoter for VDJ in naïve B cells are IgM and IgD.
b. Class switching involves changing of the antibody into a different isotype.
Here, parts of antibody-heavy chain locus on the chromosome (determining the isotype of the antibody)are removed and surrounding gene segments are rejoined t make an antibody gene which is functional and produces a different isotype of the antibody.
The DNA is nicked at 2 specific places called the Switch [S] region (conserved nucleotide motifs, by the help of enzymes like Activation Induced Deaminase (AID), Uracil DNA glycosylase and AP endonucleases. The DNA region between the S region is deleted. Rejoining of free ends of DNA occurs by non-homologous end joining.
(To answer the requirement of specific sequences, YES, The S region is that specific sequence where the DNA breaks occur)