Germinal centre cell proliferation in murine spleens
Germinal centres are dynamic structures in which a number of kinetic processes take place. This thesis was designed to investigate mechanisms whereby one of these kinetic events, germinal centre cell proliferation, is regulated in vivo. In order to achieve this, the proliferative rate of germinal centre cells was measured in C3H/HeN mice under a variety of experimental conditions. In particular, the effect on germinal centre cell proliferation of different classes of antigen and of variously timed doses of the immunosuppressant drug cyclosporin A, was examined. In some experiments, an immunohistochemical technique was employed to demonstrate the distribution of antigen within murine spleens and to correlate the presence of antigen within germinal centres with the germinal centre cell birth rate. The results showed that the type of antigen to which an animal is exposed does determine the subsequent rate of germinal centre cell proliferation. In addition it became apparent that specific regulatory mechanisms were at work within murine germinal centres which either stimulated or inhibited germinal centre cell proliferation depending on the stage of the germinal centre reaction. The proliferative response to antigen was also significantly affected by treatment of the animals with cyclosporin A. The effect of the drug varied depending on the timing of its administration in relation to antigen. These results indicated that T cell derived cytokines play a central role in regulating both stimulation and inhibition of germinal centre cell proliferation. It is proposed that interleukin-4 and interleukin-5 are involved in driving the former, while interferon-γ is a candidate for mediating the latter.