VDJ rearrangement

The adaptive immune response is highly specific for each invader, and that’s because the cells of the adaptive immune response have receptors that differentiate friendly bacteria and potentially deadly pathogens from their unique parts - called antigens.

The key cells of the adaptive immune response are the lymphocytes- the B and T cells.

And the antigen receptors for T cells and B cells have a lot of things in common, one of which is that they share the same mechanism - called VDJ rearrangement - to generate a massively diverse set of receptors.

VDJ stands for variability, diversity, and joining, respectively, and VDJ rearrangement has 4 key characteristics that help ensure that each antigen receptor is unique.

First, each individual inherits multiple V, D, and J gene segments; second, the V, D, and J gene segments randomly recombine - meaning that any V can pair with any D and any J; third, there’s recombinational inaccuracy - meaning that this process is purposefully error prone - which leads to additional variation; and fourth, there’s random reassortment of two chains - meaning that this process involves two different chains that come together to make the receptor.

First, let’s look at our antigen receptors. The B cell receptor, or BCR, is essentially an antibody, except that it has a transmembrane part that goes through the membrane and attaches the receptor to the surface of a B cell.

Just like antibodies, the B cell receptor has a heavy chain and a light chain.

One region or fragment of the B cell receptor binds the antigen and it’s called the fragment - antigen binding or Fab region.

There are two Fab regions on every B cell receptor.

Then there’s the constant region or fragment called the fragment - constant or Fc region, which is the part that determines what class of B cell receptor it will be - for example, IgM or IgD, and whether or not it will remain a membrane bound B cell receptor or if it will get secreted as a free floating antibody.

The T cell receptor, or TCR, on the other hand looks quite different but still only has two chains.

In this case it has an alpha chain which is analogous to the B cell light chain, and a beta chain which is analogous to the B cell heavy chain.

Unlike the B cell receptor, the alpha and beta chains of the T cell receptor only form a transmembrane receptor - they don’t get secreted and there aren’t different classes. They also only have one antigen binding site.