AssessmentsSomatic hypermutation and affinity maturation
Somatic hypermutation and affinity maturation
USMLE® Step 1 style questions USMLE
An activated B cell located in the spleen binds an antigen and is activated via cytokines from a nearby T cell. An enzyme is then expressed in the B cell, which causes random nucleotides to be changed in the B cell receptor variable region. Subsequent generations of daughter cells of this B cell develop progressively stronger binding to this antigen. Which of the following correctly describes this process?
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.
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.
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.
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.