The purpose of this research is to determine how substances with adjuvanticity modulate immune responses and to devise a means to control some of the potentially harmful capacities of adjuvants. Adjuvants have great potential in enhancing immune responses to weak tumor antigens. Also, adjuvant-like substances naturally present in vivo, as low levels of bacterial endotoxin of Fc fragment of immunoglobulin generated by digestion of antigen-antibody complexes, may serve to enhance day-to-day immune responses to malignant tissue and infectious agents. However, most adjuvants, in addition to augmenting immune responses, nonspecifically activate B cells which result in polyclonal antibody synthesis of unrestricted specificity and interference with tolerance induction. Both of these capacities could lead to generation of antibody to self, causing overt autoimmune disease or more subtle forms of tissues damage accumulating over the life of the individual which could exacerbate conditions as arthritis and possibly the aging process itself. This research will concentrate on purification and characterization of a non-immunoglobulin, serum regulatory factor in normal mouse serum discovered in the applicant's laboratory which appears to inhibit selectively non-specific B cell activation without affecting specific B cell activation. The goals of this research are 1) to purify the inhibitory serum component; 2) to reassess its apparent selectivity for inhibition of non-antigen-specific B cell activation; 3) to determine the mechanism of inhibition; and 4) to determine if there is an inhibitory couterpart in human plasma or serum. The effect of the purified serum factor on polycolonal antibody synthesis, interference with tolerance induction by adjuvants, and enhancement by adjuvants of various immune responses will then be assessed. The long-term objectives of the research are to prevent the potential negative consequences of adjuvants in order to take advantage of the beneficial effects of adjuvants in augmenting the immune response against infectious and malignant disease.
| Walker, S M; Alwerud, E C (1987) Serum-mediated suppression of nonspecific B-cell activation. III. Selective inhibition of the polyclonal B-cell response by normal mouse serum. Cell Immunol 107:433-42 |
| Walker, S M (1985) Abrogation of macrophage-mediated suppression of T-lymphocyte proliferation with hemoglobin and hemin is a function of iron content. Cell Immunol 90:267-73 |
