Dichotomous Effects of Complete Versus Partial Class II Major Histocompatibility Complex Deficiency on Circulating Autoantibody Levels in Autoimmune-Prone Mice

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Abstract

Objective

To assess the effects of altered class II major histocompatibility complex (MHCII) expression on circulating autoantibody levels in C57BL/6 (B6) mice congenic for the Sle1 (B6.Sle1 mice) or Nba2 (B6.Nba2 mice) regions.

Methods

H-2Ab+/+ (MHCII-intact), H-2Ab+/− (MHCII-intermediate), and H-2Ab−/− (MHCII-deficient) littermate B6.Sle1 and B6.Nba2 mice were evaluated for spleen cell phenotype, numbers of splenic Ig-secreting cells, and serum levels of total IgM, total IgG, IgG antichromatin, IgG antihistone, and IgG anti–double-stranded DNA (anti-dsDNA).

Results

Compared with their MHCII-intact littermates, MHCII-deficient B6.Sle1 and B6.Nba2 mice developed markedly decreased circulating levels of IgG autoantibodies, along with decreased circulating levels of total IgG. In sharp contrast, MHCII-intermediate mice developed increased circulating levels of IgG autoantibodies. This was associated with increased numbers of splenic Ig-secreting cells and serum levels of total IgG in B6.Sle1 mice, but it occurred without concomitant increases in the numbers of splenic Ig-secreting cells or serum total IgG levels in B6.Nba2 mice.

Conclusion

In 2 clinically healthy strains of mice with a genetic proclivity for developing autoantibodies, the effects of class II MHC expression on levels of circulating IgG autoantibodies were found to be complex. In the absence of MHCII expression, circulating IgG autoantibody levels were minimal. With full MHCII expression, circulating IgG autoantibody levels were considerable. With intermediate MHCII expression, circulating IgG autoantibody levels were even greater. These last findings may help explain why heterozygosity at the H-2 locus is associated with increased autoantibody titers and aggravated disease in certain lupus-prone mice.

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