Immunological memory and the germinal centre reaction

The immune system requires the cognate interactions of T cells, B cells, and antigen presenting cells to respond to invading antigens/pathogens. The peripheral organs where the immune response occurs are organized into microanatomic compartments that are composed of T cell zones and B cell follicles. B cell responses to thymus dependent (TD) antigens begin in the T cell zones of secondary lymphoid tissues where T and B cells initiate antigen and costimulus dependent proliferation. These initial cognate interactions are essential for humoral immunity, but alone result in only transient, low affinity antibody responses. It is a subsequent set of cellular encounters, collectively known as the germinal centre (GC) reaction, that drives affinity maturation and memory.

One of the important events taking place in GCs is the incorporation of somatic mutations in the rearranged immunoglobulin genes by a process called somatic hypermutation. Mutated Igs with high affinity for the antigen will be preferentially selected. Memory cells carrying high affinity antibodies will allow the maturation of the immune response after subsequent antigenic challenges, due to a better antigen recognition and to a faster response. Thus, a good immune reaction will drive the B cells to hypermutation.

The humoral immune response is often impaired in very young and very old people. Defective immune responses could be the result of defects in any of the several steps in antigen-driven B-cell differentiation. The immune system in newborn individuals is not well developed. In aged mice, it has been shown that the GC reaction is diminished, and the humoral immune response is often impaired. Persons 65 years and older produce significantly less Ab after immunization maintain protective titres of serum Abs for shorter periods, and generate Ab affinities typically below that of younger controls. Even when given at equivalent concentrations these Abs are less protective than those produced in young adults.

The study of these interactions and the mechanisms leading to an optimal GC reaction and the development of immunological memory what have attracted much of my attention. I have a number of projects