Immunization with a T dependent antigen induces development of germinal centers (GC) in the draining peripheral lymphoid organs. GC's are a highly organized microenvironment in which memory B cells develop. Few precursor cells undergo rapid proliferation, as well as extensive cell death, isotype switching, somatic mutation, clonal selection, affinity maturation and cellular differentiation. The characteristics of the GC that regulates these processes is unclear. Experimental approaches utilizing SCID repopulation and fragmentation culture technologies should enable the in vivo and in vitro dissection of the cellular processes involved in memory B cell generation. It is proposed to address the roles of antigen and the antigen retaining capacity of follicular dendritic cells in memory cell clonal expansion, somatic hypermutation, affinity maturation, and immune propogation. The role of Th cells will be examined as well as CD40/CD40L interactions. The stage of B cell development in which precursors of memory or antibody producing cells diverge will be examined. The cells responsible for the propagation and maintenance of memory will be studied.
The specific aims are 1) to define the role of antigen and FDC's in generating memory B cell responses, 2) to define the abilities of Th populations to facilitate memory B cell responses and 3) to define the origin of memory B cell responses.
| Linton, P J; Harbertson, J; Bradley, L M (2000) A critical role for B cells in the development of memory CD4 cells. J Immunol 165:5558-65 |
