Memory B cells are generated during the germinal center reaction and are capable of making rapid responses to subsequent introduction of antigen. Some of the B cells that are activated in germinal centers acquire the ability to survive for long periods, apparently without continuing antigenic stimulation. These memory B cells express high levels of the antiapoptotic protein BCL-2, which contributes to their long lifespan. Memory B cells exit germinal centers and recirculate between the blood and lymphoid organs. These cells typically express somatically mutated antigen receptors of intermediate affinity, and many have switched isotypes. The production of large quantities of class-switched, high-affinity antibodies is greatly accelerated after secondary exposure to antigens, and this can be attributed to the activation of memory cells. Many of the features of secondary antibody responses to protein antigens and their differences from primary responses (see Fig. 1) reflect the differences between responses of memory cells and naive B cells, respectively.
Fig1. Primary and secondary humoral immune responses. In a primary immune response, naive B cells are stimulated by antigen, become activated, and differentiate into antibody-secreting cells that produce antibodies specific for the eliciting antigen. A secondary immune response is elicited when the same antigen stimulates memory B cells, leading to production of greater quantities of specific antibody than are produced in the primary response. Note that the characteristics of secondary antibody responses summarized in the table are typical of T-dependent antibody responses to protein antigens.
Effective vaccines against microbes and microbial tox ins must induce both affinity maturation and memory B-cell formation, and these events will occur only if the vaccines are able to activate helper T cells. This concept has been applied to the design of vaccines for some bacterial infections in which the target antigen is a capsular polysaccharide, which is incapable of stimulating T cells. In these cases, the polysaccharide is covalently linked to a foreign protein to form the equivalent of a hapten-carrier conjugate, which does activate helper T cells (Fig. 2). Such vaccines, which are called conjugate vac cines, more readily induce high-affinity antibodies and memory cells than do polysaccharide vaccines without linked proteins. Conjugate vaccines have proved particularly effective at inducing protective immunity in infants and young children, who are less able to make strong T-independent responses to polysaccharides than are adults.
Fig2. Conjugate vaccines allow polysaccharides to be treated as T-dependent antigens. Conjugation of a bacterial capsular polysaccharide to a protein carrier (tetanus toxoid) facilitates the entry of B cells specific for the polysaccharide into the germinal center response and allows the generation of memory B cells and high-affinity antibodies from long-lived plasma cells. ITIM, Immunoreceptor tyrosine-based inhibition motif; PIP2, phosphatidylinositol bisphosphate; PIP3, phosphatidylinositol trisphosphate; SHIP, SH2 domain– containing inositol phosphatase.
