Biosynthesis of Immunoglobulins

Biosynthesis of Immunoglobulins

B lymphocytes and plasma cells take part in the synthesis of immunoglobulins. Resting B cells synthesize only small amounts of immunoglobulins that mainly get incorporated into cell membranes. Plasma cells, the most differentiated B cells, are specialized to produce and secrete large amounts of immunoglobulins. The synthetic capacity of the plasma cells is reflected by the abundant cytoplasm, which is extremely rich in endoplasmic reticulum.

Normally, heavy and light chains are synthesized in sepa-rate polyribosomes of the plasma cell. The amounts of heavy and light chains synthesized on the polyribosomes are usually balanced and so both types of chains are combined to produce complete Ig molecules, without excess of any given chain. The assembly of a complete Ig molecule is carried out either by asso-ciating one heavy and one light chain to form an H–L hemi-molecule, and then joining two H–L hemi-molecules to form a single complete molecule (H2L2), or by forming H2 and L2 dimers that later associate to form the complete molecule.

While free light chains can be effectively secreted from plasma cells, free heavy chains are generally not secreted. The heavy chains are synthesized and transported to the endo-plasmic reticulum, where they are glycosylated, but secretion requires combination with light chains to form a complete immunoglobulin molecule. If light chains are not synthe-sized or heavy chains are synthesized in excess, the free heavy chains combine through their CH1 domain with a heavy-chain-binding protein, which is believed to be responsible for their intracytoplasmic retention.

Both IgM and IgA are the polymeric antibodies, which have one additional polypeptide chain, the J chain. The J chain is synthesized by all plasma cells, including those that produce IgG. However, it is only incorporated to polymeric forms of IgM and IgA. It is believed that the J chain has some role in initiating polymerization. IgM proteins are assembled in two steps. First, the monomeric units are assembled. Then, five monomers and one J chain combine via covalent bonds to produce a pentam-eric molecule.