Ga. Hanley et al., CLASS-II HAPLOTYPE DIFFERENTIALLY REGULATES IMMUNE-RESPONSE IN HGCL2-TREATED MICE, Clinical immunology and immunopathology, 84(3), 1997, pp. 328-337
One of the most striking features of exposure to low doses of mercury
in mice is the high-titer haplotype-linked anti-nucleolar (ANoA) autoa
ntibody response. Mice of H-2(s) haplotype have been high responders,
while H-2(b) mice have been low. This pattern has been attributed to t
he class II molecule itself, but the poor response of F-1 crosses betw
een high and low responders raised the possibility that the anti-fibri
llarin specificity was actually due to a closely linked dominant negat
ive gene. To test the role of class II explicitly, F-1 crosses between
congenic B6.SJL (H-2(s)) and C57BL/6 (H-2(b)) mice with a targeted de
letion of I-A(beta)(b) were generated, creating mice heterozygous for
all MHC loci, but expressing only I-A(s). In comparison with B6.SJL, n
o diminution of ANoA titers was found, proving that I-A(s) itself was
responsible for susceptibility and I-A(b) for downregulation. Unlike I
-A, expression of the I-E class II molecule could not downregulate the
response in an otherwise susceptible mouse. These results suggest a c
omplicated role for class II in the regulation of a novel, environment
ally induced autoimmune response. (C) 1997 Academic Press.