B lymphocytes are derived directly from bone marrow, and their antigen-specific receptor is an immunoglobulin (Ig) or antibody. The Ig structure is now known and can be found in any standard textbook of immunology. Functionally, the molecule can be divided into a variable region, which mediates antigen recognition, and a constant region, which determines isotype and mediates effector function. The constant region of Ig heavy chain can be one of five classes M, G, D, E, and A, each of which has further numbered subclasses. The Ig molecule is named after its heavy-chain class; for instance, a molecule with a G1 heavy chain is known as IgG1. Ig has a dual function, acting as an antigen-specific receptor mediating cellular activation when displayed on the surface of a B cell, but also acting as an effector molecule in its own right. Following recognition of antigen, B cells can differentiate into plasma cells and secrete soluble 'effector' Ig into the circulation.
The variable region forms an extended antigen-binding surface at the outermost tip of the molecule, consisting of three complementary-determining loop regions (CDRs). In general, antibody and antigen interact over a large (10-20 amino acid) area, and the side-chains of the amino acids, which make up the CDRs, form multiple low-energy interactions with antigen. The combination of these interactions gives rise to a very specific, and potentially high-affinity, binding between the three-dimensional surfaces of antigen and antibody. Destruction of antigen conformation usually results in loss of recognition by antibody.
The large repertoire of the antibody response resides in the extreme variability of the amino acids which make up the three CDRs. This variability is achieved by a unique molecular mechanism which involves complex DNA rearrangements between families of multiple alternative exons, combined with a still mysterious process of selective somatic hypermutation. The variable region can be coupled to any of the heavy-chain constant-region genes, enabling an Ig molecule to maintain specificity while changing class, a process described as class-switching.
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