REGULATORY MECHANISMS IN THE IMMUNE RESPONSE

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The aim of this grant is to investigate the mechanisms whereby T cells affect B cell responses to antigen in mice. Our experiments will all be carried out in vitro where conditions can be more readily defined than in the whole animal. We will use as pure populations of cells as possible as participants in responses, since in the past experiments have been incorrectly interpreted because contaminating cells (especially T cells) have played unsuspected roles in various responses. One aim in this project will be identify nonspecific factors which contribute to stimulation of B cells. In accordance with our stated intention to prepare all reagents as cleanely as possible, we already have monoclonal sources for two important factors, interleukin-1 and interleukin-2 and plan to make hybridomas which make another important factor. Once identified and purified, the roles of these factors in B cell responses will be examined. In a separate but related series of experiments we will establish conditions required for resting (Go) B cells to move into cell cycle. In particular we will examine the features of red blood cell-bound antigens which stimulate this process in the apparent absence of T cells. We will also investigate the role of antigen-specific helper T cells, which are required for B cell activation in response to protein-bound antigens. Over the years it has been apparent that T cell stimulation of B cell responses is much more complicated than was at first thought. It is our long term objective to unravel these complexities with the hope that what is more fully understood may be more readily controlled both in mouse and man.