heavychain

Heavy chain refers to the larger polypeptide chain of antibodies, paired with a light chain to form a complete immunoglobulin molecule. The heavy chain contributes the majority of the antibody’s constant region and, together with the light chain, forms the antigen-binding site. The isotype of an antibody is defined by its heavy-chain constant region (mu, delta, gamma, alpha, epsilon), which determines effector function and tissue distribution. Each immunoglobulin molecule has two identical heavy chains and two identical light chains.

Genetics and rearrangement: The heavy chain is encoded by the IGH locus. During B cell development, V, D, and J gene segments undergo somatic recombination to assemble a variable region. The heavy-chain constant-region genes encode the five major isotypes: Cμ, Cδ, Cγ, Cα, and Cε. Naive B cells coexpress IgM and IgD, and class switch recombination can replace the constant region to produce antibodies of a different isotype while preserving antigen specificity.

Structure and function: The variable region of the heavy chain (VH) pairs with a light-chain variable region (VL) to form the antigen-binding site. The heavy-chain constant region contains CH1, CH2, and CH3 domains; the Fc portion of the heavy chain engages Fc receptors and, in certain isotypes, activates the complement system. In membrane-bound antibodies, the heavy chain includes a transmembrane region and cytoplasmic tail that anchors the B cell receptor; in secreted antibodies, the heavy chains form the Fc region of the circulating antibody.

Clinical relevance: Abnormalities in IGH gene rearrangements or translocations are common in B-cell malignancies and are used in diagnostic clonality testing.