Somatic hypermutation and affinity maturation

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.

Both B cells and T cells undergo a process called VDJ rearrangement to generate a massively diverse set of receptors.

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.

Somatic hypermutation only happens in activated B cells, and not in T cells.

This happens at sites where B cells are activated and T cells are also present- basically in germinal centers within lymph nodes and the spleen.

When B cells receive antigen stimulation by crosslinking their BCRs, they express the molecule CD40 on their surface.

Nearby helper T cells with a CD40 ligand then come along and the CD40-CD40 ligand interaction makes the B cell upregulated cytokine receptors.

The T cell then sends out cytokines which bind to these receptors, and cause various changes within the activated B cell.