In situ studies of the germinal center reaction

Germinal center (GCs) represents a remarkable lymphoid microenvironment that functions to expand and diversify antigen-reactive lymphocyte clones. Although the GC reaction is antigen dependent, GCs share many of the processes usually thought to occur during primary lymphopoiesis, including positive and negative selection, elimination of self-reactive cells, and enrichment of the repertoire of antigen receptors. The mechanisms that underlie these processes remain unknown, but it is clear that these issues may be approached genetically. Naturally arising mutants, such as lpr or gld, transgenesis, or targeted gene disruption have already proved invaluable in understanding mutation, selection, and memory. The immigrant cells proliferate to form prominent lymphoid follicles and undergo post rearrangement V-region diversification by nonreciprocal incorporation of sequence fragments from un-rearranged V exons (chickens),the introduction of point mutations (sheep), or both (rabbits). If GCs are homologous to the more primitive gut-associated lymphoid follicles of sheep, rabbits, or chickens, phylogenetic studies may also be helpful. In the future, immunologists will face the reconciliation of two views of the immune response-immunity as the interaction of regulating factors within cells and immunity as interacting cell populations. Both views provide unique insights but neither will provide a full understanding in isolation. The ability to study the population genetics of immune responses presents considerable opportunity and should prove widely useful. © 1995, Academic Press Inc.