In mammals, there are five major classes of Igs, each of which mediates a characteristic biological response following antigen binding to an antibody: IgA, IgD, IgE, IgG, and IgM, each with its own class of heavy chain—α, δ, ε, γ, and μ, respectively. IgA molecules have α chains, IgG molecules have γ chains, and so on. Moreover, there are four human IgG subclasses (IgG1, IgG2, IgG3, and IgG4), with γ1, γ2, γ3, and γ4 heavy chains, respectively. There are also two IgA subclasses in humans. In addition to the various classes and subclasses of heavy chains, higher vertebrates have two types of light chains, κ and λ, which seem to be functionally indistinguishable. Either type of light chain may be associated with any of the heavy chains, but an individual Ig molecule always contains identical light chains and identical heavy chains: an IgG molecule, for instance, may have either κ or λ light chains, but not one of each. As a result, an Ig’s antigen-binding sites are always identical (see Figure 24–22).
The various heavy chains give a distinctive conformation to the tail region of antibodies, so that each class (and subclass) has characteristic properties of its own. IgM is always the first class of Ig that a developing B cell in the bone marrow makes. It forms the BCRs on the surface of immature naïve B cells. After these cells
Figure 24–22 The b cell receptors (bCRs) and secreted antibodies made by a b cell clone. The binding of an antigen to Bcrs on either a naïve or memory B cell (together with co-stimulatory signals provided by helper T cells—not shown) activates the cell to proliferate and differentiate into effector B cells. The effector cells produce and secrete antibodies with a unique antigen-binding site, which is the same as that of the cell-surface Bcrs. Because antibodies have two identical antigen-binding sites, they can cross-link antigens, as shown for an antigen with multiple identical antigenic determinants.
Figure 24–23 A schematic drawing of a bivalent antibody molecule. The two heavy chains each have a hinge region, which, because of its flexibility, improves the efficiency with which the antibody can cross-link antigens (see Figure 24–22). The two heavy chains also form the tail of the antibody, which determines its functional properties. The heavy and light chains are held together by both covalent S–S bonds (red) and noncovalent bonds (not shown).
leave the bone marrow, they start to produce IgD BCRs as well, with the same antigen-binding site as the IgM BCRs. These cells are now called mature naïve B cells, as they can now respond to their specific foreign antigen in peripheral lymphoid organs (Figure 24–24). IgM is also the major class of antibody secreted into the blood in the early stages of a primary antibody response on first exposure to an antigen. In its secreted form, IgM is a wheel-like pentamer composed of five four-chain units, giving it a total of 10 antigen-binding sites that allow it to bind strongly to pathogens; in its antigen-bound form, IgM is highly efficient at activating complement, which is important in early antibody responses to pathogens.