21.4 The adaptive immune response: b-lymphocytes and antibodies

Antibodies were the first component of the adaptive immune response to be characterized by scientists working on the immune system. It was already known that individuals who survived a bacterial infection were immune to re-infection with the same pathogen. Early microbiologists took serum from an immune patient and mixed it with a fresh culture of the same type of bacteria, then observed the bacteria under a microscope. The bacteria became clumped in a process called agglutination. When a different bacterial species was used, the agglutination did not happen. Thus, there was something in the serum of immune individuals that could specifically bind to and agglutinate bacteria.

Scientists now know the cause of the agglutination is an antibody molecule, also called an immunoglobulin    . What is an antibody? An antibody protein is essentially a secreted form of a B cell receptor. (In fact, surface immunoglobulin is another name for the B cell receptor.) Not surprisingly, the same genes encode both the secreted antibodies and the surface immunoglobulins. One minor difference in the way these proteins are synthesized distinguishes a naïve B cell with antibody on its surface from an antibody-secreting plasma cell with no antibodies on its surface. The antibodies of the plasma cell have the exact same antigen-binding site and specificity as their B cell precursors.

There are five different classes of antibody found in humans: IgM, IgD, IgG, IgA, and IgE. Each of these has specific functions in the immune response, so by learning about them, researchers can learn about the great variety of antibody functions critical to many adaptive immune responses.

B cells do not recognize antigen in the complex fashion of T cells. B cells can recognize native, unprocessed antigen and do not require the participation of MHC molecules and antigen-presenting cells.

B cell differentiation and activation

B cells differentiate in the bone marrow. During the process of maturation, up to 100 trillion different clones of B cells are generated, which is similar to the diversity of antigen receptors seen in T cells.

B cell differentiation and the development of tolerance are not quite as well understood as it is in T cells. Central tolerance is the destruction or inactivation of B cells that recognize self-antigens in the bone marrow, and its role is critical and well established. In the process of clonal deletion    , immature B cells that bind strongly to self-antigens expressed on tissues are signaled to commit suicide by apoptosis, removing them from the population. In the process of clonal anergy    , however, B cells exposed to soluble antigen in the bone marrow are not physically deleted, but become unable to function.

Another mechanism called peripheral tolerance is a direct result of T cell tolerance. In peripheral tolerance    , functional, mature B cells leave the bone marrow but have yet to be exposed to self-antigen. Most protein antigens require signals from helper T cells (Th2) to proceed to make antibody. When a B cell binds to a self-antigen but receives no signals from a nearby Th2 cell to produce antibody, the cell is signaled to undergo apoptosis and is destroyed. This is yet another example of the control that T cells have over the adaptive immune response.