MURINE B LYMPHOCYTE DEVELOPMENT

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The purpose of this research project is to examine the capacities of lymphopoietic progenitors to generate certain antigen-reactive B cell subsets in adoptive transfer. A novel transplantation model will be employed involving unirradiated immunodeficient xid mice which are unable to mount anti-phosphorylcholine (PC) PFC responses. By using unirradiated hosts, the forced competition between the engrafted donor cells and the intact host cells for the opportunity to develop into the mature state should closely approximate the normal situation in ontogeny; by studying stem cell differentiation under relatively normal, or nondisruptive, conditions, even subtle distinctions between the regeneration abilities of precursors to different antigen-reactive subsets will be accentuated. Thus, the experimental system offers a sensitive means for analyzing the population dynamics of emerging B cell subpopulations. Furthermore, by utilizing the PC system, the ability to partition responses in terms of dominant and nondominant idiotypes will provide an additional level of discrimination. The transplantation of stem cells into precisely and minimally altered environments, and the monitoring of the related, idiotypically well-defined antigen-reactive subsets generated by the engrafted cells will provide information not only on the generation and diversification of B cell lineages, but also with respect to the clonal relationships within functionally delineated B cell compartments. We believe that our experiments will provide new information on normal and abnormal murine lymphopoiesis.