The Antibody Response to Myelin Basic Protein (BP) in Lewis Rats: The Effect of Time, Dosage of BP, and Dosage of Mycobacterium Butyricum

Abstract

Abstract Through the use of a sodium sulfate method of radioimmunoassay the influence of variables such as the dosage of myelin basic protein (BP), the dosage of Mycobacterium butyricum, and the presence or absence of Bordetella pertussis was studied with reference to time of appearance and final level of anti-BP antibody in Lewis rats. Animals injected with constant amounts of mycobacteria (250 µg) and variable amounts of BP (2 to 50 µg) in Freund's complete adjuvant showed antibody levels which were proportional to the dosage of BP injected. The appearance of experimental allergic encephalomyelitis (EAE) could not be correlated with antibody level. When doses of BP were held constant (2.5 µg) while doses of injected mycobacteria were varied (5 to 500 µg), animals receiving higher amounts of mycobacteria developed antibody later and at lower levels than animals receiving an intermediate dosage of 50 µg. Parameters found to have very little influence upon antibody levels were the administration of 6.4 × 109 B. pertussis organisms as an ancillary adjuvant and the frequency of animal bleeding. Mycobacteria control injections in complete Freund's adjuvant without BP were shown to induce anti-BP antibody formation above normal, particularly at lower doses, but adsorption studies showed no evidence for BP-mycobacteria cross-reactivity. The hypothesis was raised and discussed that a) a normal animal contains a few active B-cells which produce low levels of anti-BP antibody, that b) this non-proliferative B-cell response is antagonistic to and/or competitive with the cell-mediated EAE-producing T-cell response, that c) the injection of BP antigen and mycobacteria in high enough doses in complete Freund's adjuvant simultaneously neutralizes the normal protective responses and sets the stage for EAE, and that d) the later proliferative B-cell response usually comes too late to be inhibitory.