Immunoglobulin heavy chain

A typical antibody is composed of two immunoglobulin (Ig) heavy chains and two Ig light chains. Several different types of heavy chain exist that define the class or isotype of an antibody. These heavy chain types vary between different animals. All heavy chains contain a series of immunoglobulin domains, usually with one variable domain (V_H) that is important for binding antigen and several constant domains (C_H1, C_H2, etc.). Production of a viable heavy chain is a key step in B cell maturation. If the heavy chain is able to bind to a surrogate light chain and move to the plasma membrane, then the developing B cell can begin producing its light chain.

The heavy chain does not always have to bind to a light chain. Pre-B lymphocytes can synthesize heavy chain in the absence of light chain, which then can allow the heavy chain to bind to a heavy-chain binding protein.

In mammals

Classes

There are five types of mammalian immunoglobulin heavy chain: γ, δ, α, μ and ε. They define classes of immunoglobulins: IgG, IgD, IgA, IgM and IgE, respectively.

• Heavy chains α and γ have approximately 450 amino acids.
• Heavy chains μ and ε have approximately 550 amino acids.

Regions

Each heavy chain has two regions:

• a constant region (which is the same for all immunoglobulins of the same class but differs between classes).
  • Heavy chains γ, α and δ have a constant region composed of three tandem (in a line next to each other) immunoglobulin domains but also have a hinge region for added flexibility.
  • Heavy chains μ and ε have a constant region composed of four domains.
• a variable region that differs between different B cells, but is the same for all immunoglobulins produced by the same B cell or B cell clone. The variable domain of any heavy chain is composed of a single immunoglobulin domain. These domains are about 110 amino acids long.

Cows

Cows, specifically Bos taurus, show a variation on the general mammalian theme in which the heavy chain CDR H3 region has adapted to produce a divergent repertoire of antibodies which present a "stalk and knob" antigen interaction surface instead of the more familiar bivalent tip surface. The bovine CDR is unusually long and contains unique sequence attributes which support the production of paired cysteine residues during somatic hypermutation. Thus, where in humans the somatic hypermutation step targets the V(D)J recombination process, the target in cows is on the creation of diverse disulfide bonds and the generation of unique sets of loops which interact with antigen. A speculated evolutionary driver for this variation is the presence of a vastly more diverse microbial environment in the digestive system of the cow as a consequence of their being ruminants.