Antibodies of the other classes—IgG, IgA, and IgE—are smaller, and diffuse easily out of the blood into the tissues. IgA can form dimers (see Fig. 5.23), but IgG and IgE are always monomeric. The affinity of the individual antigen-binding sites for their antigen is therefore critical for the effectiveness of these antibodies, and most of the B cells expressing these classes have been selected in the germinal centers for their increased affinity for antigen after somatic hypermutation. IgG4 is the least abundant of the IgG subclasses, but has the unusual ability to form hybrid antibodies. One IgG4 heavy chain and attached light chain can split from the original heavy-chain dimer and reassociate with a different IgG4 heavy chain–light chain pair, forming a bivalent IgG4 antibody with two distinct antigen specificities.
IgG is the principal class of antibody in blood and extracellular fluid, whereas IgA is the principal class in secretions, the most important being those from the epithelia lining the intestinal and respiratory tracts. IgG efficiently opsonizes pathogens for engulfment by phagocytes and activates the complement system, but IgA is a less potent opsonin and a weak activator of complement. IgG operates mainly in the tissues, where accessory cells and molecules are available, whereas dimeric IgA operates mainly on epithelial surfaces, where complement and phagocytes are not normally present; therefore IgA functions chiefly as a neutralizing antibody. Monomeric IgA can be produced by plasma cells that differentiate from class-switched B cells in lymph nodes and spleen, and it acts as a neutralizing antibody in extracellular spaces and in the blood. This monomeric IgA is predominantly of the subclass IgA1; the ratio of IgA1 to IgA2 in the blood is 10:1. The IgA antibodies produced by plasma cells in the gut are dimeric and predominantly of subclass IgA2; the ratio of IgA2 to IgA1 in the gut is 3:2.
Finally, IgE antibody is present only at very low levels in blood or extracellular fluid, but is bound avidly by receptors on mast cells that are found just beneath the skin and mucosa and along blood vessels in connective tissue. Antigen binding to this cell-associated IgE triggers mast cells to release powerful chemical mediators that induce reactions such as coughing, sneezing, and vomiting, which in turn can expel infectious agents, as discussed later in this chapter.
10-16 Polymeric immunoglobulin receptor binds to the Fc regions of IgA and IgM and transports them across epithelial barriers.