Mitogen driven differentiation of mononuclear cells is a useful model of antibody synthesis and secretion in humans. We have studied Pokeweed mitogen (PWM) induced immunoglobulin secretion in vitro in both healthy individuals and multiple sclerosis patients. Within the healthy population we have identified individuals who consistently secrete low levels of IgG in response to PWM and others who secrete very high levels. The underlying mechanisms involved in low response are not well understood. We have observed that the peripheral blood mononuclear cells (PBMC) obtained from low responders differ from those obtained from high responders in each of the following: Their T-helper cell subset contains a higher ratio of T suppressor-inducer cells over T helper-inducer cells; their PBMC contain a higher level of in vivo radiation-sensitive suppression; their PBMC generate a lower autologous mixed lymphocyte response; and their B lymphocytes secrete lower amounts of IgG when mixed with heterologous high responder T helper cells. These results suggest the response involves the interactions between T helper cell subsets, T suppressor cells and B lymphocytes and that the level of response is the sum of the contribution of each subset. PWM induced immunoglobulin secretion was measured in multiple sclerosis patients during different phases of clinical disease activity. Relapsing-remitting multiple sclerosis patients in early relapse secreted less immunoglobulin than patients with prolonged relapse, suggesting that immune function varies with clinical disease activity. Testing the level of PWM induced immunoglobulin secretion in relapsing-remitting multiple sclerosis patients during the clinically stable phase suggested that those patients who secreted high levels of IgG in response to PWM were more likely to suffer a clinical relapse within 6 months than those patients who secreted a low amount. Chronic progressive multiple sclerosis patients secreted higher amounts of immunoglobulin in this assay than healthy control individuals. This group of multiple sclerosis patients also had; (i) reduced Concanavalin A (Con A) suppressor cell activity measured both by the ability to suppress a/ Con A induced proliferation and b/ PWM induced IgG secretion in heterologous cell cultures and; (ii) reduced percentages of T cells expressing T suppressor and T suppressor-inducer markers. The treatment of chronic progressive multiple sclerosis patients in vivo with lymphoblastoid interferon resulted in a dramatic reduction in level of PWM induced immunoglobulin secretion without alteration in Concanavalin A induced suppression or in the percentages of T cells expressing subset specific markers. The PWM induced IgG secretion assay is a valuable technique for investigating the regulation of humoral immunity in both health and disease. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

An in vitro IgG secretion assay was developed to investigate the regulation of the humoral immune response in humans. Pokeweed mitogen (PWM), a plant lectin derived from Phytolacca americana stimulates human peripheral blood mononuclear cells (PBMNC) to divide and resting B-lymphocytes to differentiate into immunoglobulin secreting cells (ISC). This differentiation requires that both monocytes and T-lymphocytes be present in the culture system. The amount of IgG secreted by these differentiated B-lymphocytes in response to PWM appears to be the net result of a balance between the functional activity of the regulatory T-helper and T-suppressor cells. Alterations, qualitative or quantitative in any of these leukocyte subsets could conceivably alter the amount of IgG secreted by the B-lymphocyte subpopulation. We have employed this assay to investigate the immune status in a group of chronic progressive multiple sclerosis (MS) patients and to assess the immunoregulatory effects of interferon (Wellferon R, INF) administered in vivo to this selected group. Their mononuclear cells (MNC) were studied in this PWM induced IgG secretion assay before INF treatment and again after 7 days of daily sub-cutaneous injections (5 X 10⁶ u/day). Twenty patients received the interferon (INF) preparation and eighteen received normal saline. The study was carried out in a double blind manner and the code was broken only after individual results had been calculated. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

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