It is hypothesized that a significant subset of natural killer (NK) cells recognize target structures on lymphocytes and other hematopoietic progeny that are expressed at a specific stage of their differentiation (or state of activation). B-cell differentiation and activation has been chosen as a model system to test this hypothesis. Preliminary experiments indicate that common target structures are expressed in significant amounts at a late stage of B-cell differentiation/activation. It is not yet clear whether increased expression of these target structures depends on the stage of B-cell differentiation or their state of activation. The objectives of this proposal are to detemrine precisely when the expression of NK target structures increase during B cell differentiation and activation, what regulates the level of NK target structure(s) expressed, and what is the chemical nature of these components. For this purpose the differentiation and activation of peripheral blood B cells (predominantly B1+B2+, mid-stage of differentiation) to terminally-differentiated, immunoglobulin-secreting cells will be studied. Anti-immunoglobulin with/without sources of B-cell growth and differentiation factors will be used to study B-cell maturation in discrete steps. [Factor-responsive B-cell lines may also be used in this study.] Changes in B-cell-surface phenotype, the secretion of immunoglobulins and the level of NK target structure expression will be determined. As an alternative to cellular assays to detect changes in NK target structure expression a monoclonal antibody to these structures has tentatively been identified. This reagent and others to be developed in the course of this proposed studies will be used to study changes in the expression of NK target structures and other components coordinately expressed with them. These antibodies will also be used to characterize these components chemically. These studies whould have significance to both clinical studies related to late-stage B-cell malignancies and an understanding of the role of NK cells in B-cell differentiation and activation.
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