AssessmentsSomatic hypermutation and affinity maturation
Somatic hypermutation and affinity maturation
Activation Induced cytidine deaminase (AID) can only bind to DNA, which means it could only target genes being actively transcribed.
Content Reviewers:Rishi Desai, MD, MPH
The immune response is highly specific for each invader, and that’s because the cells of the adaptive immune response have unique receptors that can differentiate friendly bacteria from deadly pathogens by their unique parts - called antigens.
The key cells of the adaptive immune response are the lymphocytes - the B and T cells which have unique antigen receptors known as the B cell receptor or BCR and T cell receptor or TCR respectively.
B cells can further enhance the diversity of their BCR repertoire using a process called somatic hypermutation, and the result is that the cells that emerge will have a stronger and more specific response to the antigen - and this is called affinity maturation.
Now remember, that the B cell receptor is essentially an antibody except that it’s attached to the surface of the B cell.
And each B cell receptor or antibody has two general parts- the variable region which binds antigen and the constant region which determines the specific antibody class - IgM, IgG, IgA, IgD, or IgE.
When B cell receptors are initially created it’s done in the absence of antigen.
When B cells receive antigen stimulation by crosslinking their BCRs, they express the molecule CD40 on their surface.
One key change is activation of the enzyme Activation Induced cytidine deaminase or AID - an enzyme that’s only found in B cells.
Because of the role that AID plays in class switching, people who lack AID suffer from a type of Hyper IgM immunodeficiency where they have a hard time making antibodies other than IgM.
In addition to promoting class switching, AID also leads to somatic hypermutation.
You see, AID can only bind to single-stranded DNA, so it’s really only able to target genes that are being actively transcribed during the rapid proliferation phase that occurs following B cell activation.
The way the AID enzyme works is turning a cytidine into a uridine in the DNA.
Now keep in mind that uridine is completely foreign to DNA and typically only found in RNA.
And uridine can’t properly bind to the guanosine nucleoside on the opposite DNA strand.
As a result, the cell tries to fix this mistake in the DNA in one of two ways - either mismatch repair or base excision repair.