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.
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