Synthesis Assembly and Secretion of Immunoglobulins

Immunoglobulin heavy- and light-chain mRNAs are translated on separate polyribosomes of the rough endoplasmic reticulum (RER). Newly synthesized chains contain an amino-terminal leader sequence, which serves to guide the chains into the lumen of the RER, where the signal sequence is then cleaved. The assembly of light (L) and heavy (H) chains into the disulfide-linked and glycosylated immunoglobulin molecule occurs as the chains pass through the cisternae of the RER. The complete molecules are transported to the Golgi apparatus and then into secretory vesicles, which fuse with the plasma membrane (Figure 5-18).

The order of chain assembly varies among the im-munoglobulin classes. In the case of IgM, the H and L chains assemble within the RER to form half-molecules, and then two half-molecules assemble to form the complete molecule. In the case of IgG, two H chains assemble, then an H2L intermediate is assembled, and finally the complete H2L2 molecule is formed. Interchain disulfide bonds are formed, and the polypeptides are glycosylated as they move through the Golgi apparatus.

If the molecule contains the transmembrane sequence of the membrane form, it becomes anchored in the membrane of a secretory vesicle and is inserted into the plasma membrane as the vesicle fuses with the plasma membrane (see Figure 5-18, insert). If the molecule contains the hydrophilic sequence of secreted immunoglobulins, it is transported as a free molecule in a secretory vesicle and is released from the cell when the vesicle fuses with the plasma membrane.

Immunoglobulin Synthesis
Secreted Ig

Trans Golgi reticulum

Trans Golgi

Cis Golgi

Trans Golgi reticulum

Trans Golgi

Cis Golgi

Secretion Immunoglobulins

Light-chain translation

Nascent Ig (leader cleaved)

Heavy-chain translation

Light-chain translation

Nascent Ig (leader cleaved)

Heavy-chain translation

FIGURE 5-18

Synthesis, assembly, and secretion of the immunoglobulin molecule. The heavy and light chains are synthesized on separate polyribosomes (polysomes). The assembly of the chains to form the disulfide-linked immunoglobulin molecule occurs as the chains pass through the cisternae of the rough endoplasmic reticulum (RER) into the Golgi apparatus and then into secretory vesicles. The main figure depicts assembly of a secreted antibody. The inset depicts a membrane-bound antibody, which contains the carboxyl-terminal transmembrane segment. This form becomes anchored in the membrane of secretory vesicles and then is inserted into the cell membrane when the vesicles fuse with the membrane.

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