Human recipients of autologous or allogeneic bone marrow invariably suffer from the inability to respond to specific antigenic challenge. a condition that persists well beyond the time of recovery of normal levels of immunogiobulins. We extend the hypothesis that mature donor-derived, membrane (m) Ig+ beta cells stably engraft in the immunocompromised host and influence the immune competence of the host. Human clinical trials indicate that donor and/or host immunization improves the immune response of the host to specific antigen, supporting the hypothesis that conditions that favor the engraftment of mature beta cells favor the development of specific immune competence. Requirements to achieve mature beta cell engraftment can be best studied in the neonate where there appears to be a """"""""barrier"""""""" to the engraftment of beta cell progenitors. Data presented indicates that deliberate antigenic challenge shortly after transfer was required to establish clones of mlg+ cells with desired specificities. However, even in the absence of deliberate antigenic challenge, donor beta cells engrafted. This suggested that environmental or autoantigens may have had a significant impact on engraftment of donor-derived mlg+ beta cells with specificity to auto- or environmental antigens. Adoptive transfer experiments into irradiated adults have indicated that beta cell progenitors and mIg+ cells may compete for colonization, The outcome of this competition may have a profound impact on the ultimate humoral immune competence of the transplanted host. The balance between the mlg+ and progenitor cell engraftment may be influenced by T cell help, providing a stimulus for mature beta cell engraftment, at the expense of progenitor cell engraftment. The result would be a severely limited repertoire, skewed to the expression of specificities expressed by the mature beta cells. Experiments are proposed to critically evaluate the conditions that alter the course of progenitor and mature beta cell engraftment in the immunocompromised host. Emphasis will be placed on the diversity and functional capabilities of donor and host beta lymphocytes in chimeric mice. Since T cells appear to improve the engraftment of mature beta cells, the precise function of T cells in beta cell will be elucidated. Alternative strategies to enhance beta cell engraftment by in vitro immunization, activation with mitogens and immunological studies that will provide insights into the development and implementation of strategies to improve beta cell Immunocompetence in the human bone marrow transplant recipient.
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