Antibody classes

The immune response is highly specific for each invader, and that’s because the cells of the adaptive immune response have unique receptors that are able to differentiate friendly bacteria from potentially deadly pathogens by their unique parts - called antigens. The key cells of the adaptive immune response are the lymphocytes - the B and T cells. B cells develop in the bone marrow where they undergo a process called VDJ rearrangement to generate a massively diverse set of B cell receptors.

The B cell receptor is essentially an antibody except that it has a transmembrane part that goes through the membrane attaching the receptor to the surface of the B cell. The B cell receptor, has two heavy chains and two light chains, and the region or fragment of the B cell receptor that binds the antigen is called the fragment-antigen binding or Fab region. The Fab region is where the ends of the heavy and light chains meet, and there are two Fab fragments on each B cell receptor. The remainder of the heavy chain makes up the constant region or constant fragment region, also called Fc. The two heavy chains are linked to one another by disulfide bonds and each heavy chain is also linked to a light chain by a disulfide bond. Each B cell receptor, has two identical heavy and light chains, resulting in two identical antigen binding sites.

As the B cell develops into a plasma cell, the B cell receptor gets secreted as an antibody with the exact same antigen specificity. However, the heavy chain actually changes as the B cell develops. There are 5 major types of heavy chains which encode the isotypes or classes of immunoglobulins: IgM, IgD, IgG, IgA, and IgE. These five are encoded by heavy chain genes which are referred to by the greek letters mu, delta, gamma, alpha, and epsilon. Each of these immunoglobulins has a different function, shape, and consequently valence. The valence of an antibody is the amount of antigen binding or Fab fragments it has.

Immunoglobulin M, or IgM, is the first antibody response made in all immune responses. It makes up approximately 4% of the immunoglobulin found in the serum. This is because it serves as the the B cell receptor, and like a transformer, it has two completely different conformations.

When it’s serving as the B cell receptor it’s a monomer, and it has a valence of 2 meaning that it has two Fab regions. When IgM is secreted from a plasma cell it joins up with four other identical IgM antibodies, making a total of 5 antibodies that form a pentamer that’s held together by a J or joining chain. The J chain is a 15 kDa polypeptide chain that promotes the polymerization of the pentamer by covalently linking to the cysteines of the tails of the Fc regions of the IgM molecule. Because it’s a pentamer, secreted IgM has a valence of 10.

IgM is the first type of antibody produced in a primary immune response, meaning the first time you see a pathogen. Unlike all of the other antibodies, IgM can be made without T cell help, which also means that IgM doesn’t rely on a peptide antigen, and can even work against carbohydrates and lipids antigens. Finally, IgM is the most effective antibody at activating the complement pathway which is particularly helpful in fighting bacterial infections.

IgG is the most abundant immunoglobulin, making up 75% of the immunoglobulin found in serum! The IgG molecule is a monomer made up of two gamma heavy chains and two light chains, so its valence is 2. There are four subclasses of IgG molecules - IgG1, IgG2, IgG3, and IgG4 - and they have slight differences in their constant regions but all still make IgG molecules.

The most important role of IgG is to serve as an opsonin, and in general opsonins are terrific because they help phagocytes get a firm grip on bacteria. Normally, bacteria have an antiphagocytic capsule which makes them slippery and hard to grab. Opsonization is the process by which pathogens are coated with molecules so that they can be more easily picked up and eaten by phagocytes. Imagine trying to pick up a slippery meatball with your fingers versus stabbing it with a fork and then just having to pick up the fork.

Opsonization also makes it easier to eat meatballs faster too. In this case, IgG is serving as that fork, and the phagocyte has a receptor for IgG, knows as Fc gamma receptor, which allows it to bind to - or hold the fork. IgG is also great at activating the classical complement pathway, which helps destroy extracellular pathogens like bacteria.

For intracellular pathogens, like viruses, IgG works with natural killer, or NK, cells to perform antibody dependent cell mediated cytotoxicity, or ADCC.

In ADCC, IgG binds to specific antigens, typically viral antigens, that are expressed on the surface of target cells.

The NK cell then uses the molecule CD16, which is on its surface, to bind to the antibodies. This causes the NK cell to release granzymes and perforin that kill the target cell. Finally, IgG is the only antibody that can cross the placenta, so newborn babies are born with lots of maternal IgG that provides protection during the first 6 months of life.

IgA makes up about 20% of the serum immunoglobulin - and there it exists as a monomer with a valence of 2. Unlike IgG, it’s unable to cross the placenta and it’s unable to activate the classical or alternative complement pathways.