Purpose of Fc Region

Question

Could someone explain to me the role played by the Fc region of an antibody as well as the purpose of isotype switching? According to Wikipedia, it's to allow the antibody to be usable by different Fc receptors, but I don't get what Fc receptors are for.

For context,

1. I'm reading about affinity maturation and learning about how ecological and evolutionary processes --- division, selection, and mutation --- drive the maturation of B cells leading to high-affinity plasmocytes that can better target a foreign antigen. Because all this happens on the Fab fragment, it makes sense to me why the Fab region is important in the antibody.
2. I'm not trained in cell biology.
3. My goal is to understand the general purpose of the Fc region and how isotype switching may be a major determinant for specific immunological or physiological outcomes, although I'd love to hear anything interesting!

Thanks in advance!

Answer 1

Preamble

From the point of view of understanding I think it is better to talk about the constant and variable regions of antibodies, rather than Fab and Fc, as these are historical designations for fragments of the molecules that were useful in research, but do not exist as separate entities.

Cartoon representation

It is possible to represent the immunoglobulin molecule diagrammatically as shown below. In the left-hand diagram V = variable and C = constant, and the suffixes H and L refer to the heavy and light chains. The right-hand diagram, which purports to be more three-dimensional, shows how the variable regions are responsible for binding the antigen — different manifestations of the variable region have different antigen-specificity.

The different iotypes for an immunoglobulin with a particular antigen-specificity are shown next, with a pre-colour scheme that focuses on the difference between the constant regions of each isotype.

Functions of the constant region of different isotypes

The variable region of an immunoglobulin does the exciting stuff — it binds an antigen, but that is not sufficient for its action. As well as the specific discriminatory action of the variable region, there are roles in presentation and disposal that are the same for all antibodies of a class, but may differ between classes. That is what the constant regions do.

I am not an immunologist (although had to teach the biochemistry at one time in my life — hence the diagrams) so the examples I present are simplistic and incomplete. However here are a few:

• IgM is made early in the immune response and hence is not very abundant. In order to enhance its response it forms pentamers in which the constant region of the heavy chain interacts with an additional J chain.
• IgA is involved in immune protection in mucous regions of the body exposed to the exterior. It is directed there by interaction with a receptor on the appropriate epithelial cells, which binds the constant regions of an IgA dimer attached to a J chain.
• IgE stimulates mast cells to produce histamine. These mast cells have receptors for the constant region of the heavy chains of IgE.

There are many sources on line dealing with this topic, including a section in Berg et al. that has a similar structural approach to that presented here.

Answer 2

The Fc region is composed of the two heavy chain constant regions, and its amino acid composition differs between the different classes of immunoglobulin (antibody). The Fc region of the five immunoglobulin (Ig) classes (IgA, D, E, G, and M)confers upon each class of Ig certain capabilities or properties. For example, IgG can cross the placenta, has a long half-life in serum, and it is opsonic (i.e., binds to Fc-gamma receptors on macrophages, facilitating phagocytosis of microbes), IgE binds to mast cells stimulating hayfever-type allergies, IgA is secreted onto mucosal surfaces, and IgM (and IgG) can activate the complement system, etc.

Answer 3

1.The Fc region is used as binding site for different immune system cells after the opsonisation of a pathogen. 2.Complement protein C1 binds to Fc region of antibody bound to an antigen to trigger classical complement pathway which leads to destruction of that antigen-antibody complex or opsonised pathogen