A single dose of pasteurized Mycobacterium bovis administered intravenously to prediabetic non-obese diabetic (NOD) mice prevented the onset of
type 1 diabetes but precipitated a systemic 'autoimmune
rheumatic disease' (ARD) similar to
systemic lupus erythematosus. This syndrome was characterized by
haemolytic anaemia, anti-dsDNA and anti-Smith
antigen (Sm)
antinuclear autoantibodies, increased severity of
sialadenitis and glomerular
immune complex deposition. Here, we examine the specificity of the
autoantibody responses in M. bovis-treated NOD mice. Large amounts of antibody were detected to the Sm/
ribonucleoprotein (RNP) complex, of which the 28 000 MW
polypeptide appeared to be immunodominant. The
IgG subclass involved in the anti-Sm response was primarily
IgG2a.
Antibodies against dsDNA were also detected, but the subclass of this response was mixed, with
IgG2a and
IgG2b being present in equal amounts. Together, these findings argue against a role for immune deviation towards T helper type 2 (Th2) responses in pathogenesis of the disease. The anti-dsDNA and anti-Sm reactivities were not mediated by polyreactive
antibodies since neither
antigen could cross-compete plasma antibody binding to the other in competitive
enzyme-linked
immunosorbent assay. The role of polyclonal B-cell activation was examined by measuring total
gamma-globulin as well as
IgG reactive with other
nuclear antigens including Ro60, Ro52 and La, which although not a major component of the
autoantibody responses in these mice, did show small but significant increases following immunization with M. bovis. Thus polyclonal stimulation, while likely to be occurring, was not directly responsible for production of anti-Sm
antibodies.