Heavy chain

Heavy chain refers to the larger polypeptide subunit of an antibody (or immunoglobulin) molecule. Antibodies are crucial components of the immune system, playing a key role in identifying and neutralizing foreign objects like bacteria and viruses. Each antibody molecule is composed of two heavy chains and two light chains, linked together by disulfide bonds. The specific structure of the heavy chain determines the class or isotype of the antibody, which can influence its function and location within the body.

Structure and Function

The heavy chain in an antibody contains a variable region (VH) at one end, which is responsible for antigen binding, and a constant region (CH) that determines the antibody's isotype and mediates its effector functions. The variable region of the heavy chain pairs with the variable region of a light chain to form the antigen-binding site of the antibody. The constant region, on the other hand, interacts with other components of the immune system, such as complement proteins and various cell receptors, to initiate the destruction or removal of the antigen.

Isotypes

In humans, there are five main isotypes of antibody heavy chains, corresponding to the five classes of antibodies: IgA, IgD, IgE, IgG, and IgM. Each isotype has a distinct function and distribution within the body:

• IgA: Found mainly in mucosal areas, such as the gut, respiratory tract, and urogenital tract, as well as in saliva, tears, and breast milk. It plays a crucial role in mucosal immunity.
• IgD: Mainly found on the surface of immature B cells and plays a role in the initiation of immune responses.
• IgE: Associated with allergic reactions and defense against parasitic infections.
• IgG: The most abundant antibody in blood and extracellular fluid, providing the majority of antibody-based immunity against invading pathogens.
• IgM: Expressed on the surface of B cells and secreted into the blood and lymph. It is the first antibody to be made by the body to fight a new infection.

Genetics

The genetic information for heavy chain production is located on chromosome 14 in humans. The heavy chain gene locus is complex, containing multiple variable (V), diversity (D), and joining (J) gene segments, which undergo somatic recombination to create the diverse range of antibodies necessary for the immune system to recognize a vast array of antigens.

Clinical Significance

Alterations in heavy chain production can lead to various diseases. For example, heavy chain diseases are a rare group of immunoproliferative disorders characterized by the overproduction of abnormal heavy chains or fragments thereof. Additionally, certain forms of cancer, such as multiple myeloma, involve the proliferation of cells that produce abnormal antibodies, including defective heavy chains.