The events leading to B lymphocyte activation are strongly dictated by the cell's developmental stage and perhaps its maturational history. For mature B cells, cell interactions between B cells and T cells can lead to B cell growth, proliferation, and secretion of antibody. Extensive analyses of these interactions have suggested T cell recognition of B-cell surface antigens is essential for effective communication. Subsets of helper T cells have been defined which interact with unique B-cell surface antigens and which deliver signals influencing the quantity and the type of antibody secreted by a population of B cells. Upon close examination, the activation of a B cell by subsets of helper T cells depends not only on the expression but also the density of the appropriate cell surface antigen, suggesting strongly that there is direct communication between T and B lymphocytes in generating an antibody response. It might be suggested that the direct T B cell interactions need not be confined to laboratory analyses but may play an integral role in influencing B cell maturation in vivo, particularly in the presence of environmental antigens. We intend to study three of the elements controlling the interactions of subsets of T cells and B cells: Ia antigens, immunoglobulin idiotypic determinants, and antigen. The responses will be analyzed using defined, monoclonal populations of cells and measuring B cell activation to secretion in response to phosphorylcholine--an antigen found commonly as a component of respiratory and gut flora. To evaluate B cell activation, we will use both functional assays looking for proliferation and secretion and will look for the correlation of the expression of cell surface markers and cell size. Finally, we intend to demonstrate that those elements in the environment which can directly interact with a B cell may influence its maturation, changing its subsequent activation requirements and skewing its frequency of representation in the total B-cell pool. Thus, we are particularly interested in determining whether or not B cells raised in the absence of particular T-cell subsets and/or environmental antigen will differ in their activation requirements. (LB)
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