During a primary adaptive immune response to an antigen, lymphocytes that recognize the antigen proliferate so that there are more of them to respond the next time, during a secondary response to the same antigen; moreover, during a primary response, some lymphocytes differentiate into memory cells, which can respond faster and more efficiently the next time the same pathogen invades. These two mechanisms are largely responsible for immunological memory. Both B and T cells circulate continuously between one peripheral lymphoid organ and another via the blood and lymph; only if they encounter their specific foreign antigen in a peripheral lymphoid organ do they stop migrating, proliferate, and differentiate into effector cells or memory cells. Lymphocytes that would react against self molecules either alter their receptors (in the case of B cells) or are eliminated or inactivated; they can also be suppressed by regulatory T cells. These mechanisms collectively are responsible for immunological self‑tolerance, which ensures that the adaptive immune system normally avoids attacking the molecules and cells of the host.
Vertebrates inevitably die of infection if they are unable to make antibodies. Antibodies are secreted proteins that defend us against extracellular pathogens in several ways. They bind to viruses and microbial toxins, thereby preventing them from binding to and damaging host cells (see Figure 24–2). When bound to an extracellular pathogen or its products, antibodies also recruit some of the components of the innate immune system, including various types of leukocytes and components of the complement system, which work together to inactivate or eliminate the invaders.
Synthesized exclusively by B cells, antibodies are produced in billions of forms, each with a different amino acid sequence. They belong to the class of proteins called immunoglobulins (abbreviated as Igs) and are among the most abundant protein components in the blood. In this section, we discuss the structure and function of immunoglobulins and how they are made in so many different forms.
B cells Make Immunoglobulins (Igs) as Both cell-Surface Antigen receptors and Secreted Antibodies
The first Igs made by a newly formed B cell are not secreted but are instead inserted into the plasma membrane, where they serve as receptors for antigen. They are called B cell receptors (BCRs), and each B cell has approximately 105 of them in its plasma membrane. Each BCR is stably associated with invariant trans-membrane proteins that activate intracellular signaling pathways when antigen binds to the BCR; we discuss these invariant proteins later, when we consider how B cells are activated with the assistance of helper T cells.
Each B cell clone produces a single species of BCR, with a unique antigen-binding site. When an antigen and a helper T cell activate a naïve or a memory B cell, the B cell proliferates and differentiates into an effector cell, which then produces and secretes large amounts of soluble (rather than membrane-bound) Ig. The secreted Ig is now called an antibody, and it has the same unique antigen-binding site as the BCR (Figure 24–22).
A typical Ig molecule is bivalent, with two identical antigen-binding sites. It consists of four polypeptide chains—two identical light chains and two identical heavy chains. The N-terminal parts of both light and heavy chains usually cooperate to form the antigen-binding surface, while the more C-terminal parts of the heavy chains form the tail of the Y-shaped protein (Figure 24–23). The tail mediates many of the activities of antibodies, and antibodies with the same antigen-binding sites can have any one of a number of different tail regions, each of which gives the antibody different functional properties, such as the ability to activate complement or to bind to receptor proteins on phagocytic cells that bind a specific type of antibody tail.
Mammals Make Five classes of Igs