For the induction of immune responses to T cell dependent antigens there is an obligatory role for B cells to interact with T cells either directly or indirectly via the production of lymphokines. Whether T cells or the thymus are able to influence the early stages of B cell development via antigen dependent or independent pathways is an issue that has not been adequately addressed. Although athymic nude mice have provided a valuable tool for studying some aspects of T cell independent modes of B cell development and activation they are not the ideal model for studying T cell regulation of B cell development. We therefore propose to design alternative in vivo models in order to examine the role of various T cell subsets and/or the role of the thymus in B cell development. We will pursue four major approaches: 1) Newborn mice will be suppressed from birth with monoclonal anti- T cell antibodies of different specificities either after neonatal thymectomy or without prior thymectomy; 2) Two different strains of immune defective mice which lack a major subset of B cells will be suppressed from birth with monoclonal anti-T cell antibodies either without or with prior neonatal thymectomy. We have previously demonstrated that such immune defective B cells (Lyb5-) may be more dependent than normal Lyb5+ B cells on T cell help for progression of normal B cell development; 3) X- irradiated thymectomized mice that have been reconstituted with bone marrow or fetal liver cells obtained from normal or immune defective mice will be suppressed with anti-T cell antibodies, and 4) To further explore our previous findings demonstrating a role for Ia dependent T cell help in B cell development we will suppress mice from birth with anti-Ia antibody then cease administration of this antibody at a time when B cell development is suppressed and determine whether combined thymectomy and administration of anti-T cell antibodies will maintain this state of B cell suppression. B cell function at various times after birth or after bone marrow transplantation will be studied in the above models with in vitro and in vivo assays that measure different aspects of B cell activation. These experiments will clarify the extent to which development of Lyb5+ or Lyb5- B cells is dependent on T cell or thymic influence.
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