This research is designed to explore mechanisms of immunologic unresponsiveness in immature and immunodeficient humans. While abnormal immune responses have been attributed to """"""""immaturity"""""""" of lymphoid cells in the normal newborn and to """"""""differentiation defects"""""""" in patients with primary immunodeficiency, in neither case has the true nature of the impaired responsiveness been delineated. The research in this proposal and maternal T and B cell phenotypes and their functional capacities to determine whether 1) B cell unresponsvieness in newborn and/or immunodeficient hosts are associated with immature B cell phenotypes or T cells with immature or dual differentiation antigens and, if so, whether the nature of the defect is similar in the two situations, 2) functional capacities of phenotypically similar cells are the same in newborn, maternal and immunodeficient hosts, and 3) the removal of excessive numbers of monocytes from in vitro culture systems will allow expression of functional capacities of such subjects' B cells not heretofore recognized. Methods to be employed include 1) phenotypic analysis of B cell surface isotypes by immunofluorescence and of T cells by cytofluorography, using a panel of monoclonal antibodies to mature and immature T cell differentiation antigens and 2) functional studies of help and suppression using an in vitro immunoglobulin synthesis assay and a reverse plaque-forming cell assay. The results of these studies should reveal the contribution (or lack of it) of immature or arrested differentiation to the impaired responsiveness present in these situations. This information should provide guidance for continuing efforts to elucidate primary biologic errors in immunodeficiency and to design more effective immunization protocols for immature humans.
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