Figure 24–24 Stages of b cell development. All of the stages shown occur before the cells bind their specific antigen. The first cells in the B cell lineage that make Ig are called pro-B cells; they make μ heavy chains, which remain in the endoplasmic reticulum until a special type of light chain is made called a surrogate light chain. The surrogate light chains substitute for genuine light chains and assemble with μ chains to form a receptor molecule that inserts into the plasma membrane. The cells are now called pre-B cells. Signaling from this pre-B cell receptor allows the cells to make bona fide light chains, which combine with μ chains to form four-chain IgM molecules that serve as cell-surface Bcrs on immature naïve B cells. After these cells leave the bone marrow, they start to express IgD Bcrs as well, which have the same antigen-binding sites as the IgM Bcrs; it is this mature naïve B cell that reacts with its specific foreign antigen in peripheral lymphoid organs.
Ig Light and heavy chains consist of constant and Variable regions
Both light and heavy chains have a variable amino acid sequence at their N-terminal ends but a constant sequence at their C-terminal ends. Whereas the constant region and variable region of a light chain are the same size, the constant region of a heavy chain is about three or four times longer, depending on the class (Figure 24–25).
The variable regions of the light and heavy chains come together to form the antigen-binding sites, and the variability of their amino acid sequences provides the structural basis for the diversity of these binding sites. The greatest diversity occurs in three small hypervariable regions in the variable regions of both light and heavy chains. Only about 5–10 amino acids in each hypervariable region form the actual antigen-binding site (Figure 24–26). As a result, the size of the antigenic determinant that an Ig molecule recognizes is generally comparably small: it can consist of fewer than 10 amino acids on the surface of a globular protein, for example (see Figure 24–22).
Both light and heavy chains are made up of repeating segments—each about 110 amino acids long and each containing one intrachain disulfide bond. Each repeating segment folds independently to form a compact functional unit called an immunoglobulin (Ig) domain. As shown in Figure 24–27A, a light chain consists of one variable (VL) and one constant (CL) domain, whereas a heavy chain has one variable and three or four constant domains: the variable domains of the light and heavy chains pair to form the antigen-binding region. Each Ig domain has a very similar three-dimensional structure, consisting of a sandwich of two β
Figure 24–25 Constant and variable regions of Ig chains. The variable regions of the light and heavy chains form the antigen-binding sites, while the constant regions of the heavy chains determine the other biological properties of an Ig protein. The different subclasses of IgG antibodies have different γ-chain constant regions.
variable region hypervariable regions Figure 24–26 Ig hypervariable regions. of heavy chain of heavy chain highly schematized drawing of how the three hypervariable regions in each light and heavy chain together form each antigen-binding site of an Ig protein.
sheets held together by a disulfide bond; the variable domains are unique in that each has its particular set of hypervariable regions, which are arranged in three hypervariable loops that cluster together at the ends of the variable domains to form the antigen-binding site (Figure 24–27B).
Even in the absence of antigen stimulation, a human can probably make more than 1012 different Ig molecules—its preimmune, primary Ig repertoire. The primary repertoire consists of IgM and IgD proteins and is apparently large enough to ensure that there will be an antigen-binding site to fit almost any potential