1. ¹Department of Pathology, University of Western Australia and Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, Perth, Western Australia, Australia
2. ²The Walter and Eliza Hall Institute of Medical Research, Post Office Royal Melbourne Hospital, Melbourne, Victoria, Australia

Correspondence: Mr VB Matthews, Biochemistry Institute, Christian-Albrechts University, Olshausen Str. 40, Kiel, 24098, Germany. Email: vmatthews@biochem.uni-kiel.de

Received 30 April 2001; Accepted 25 June 2001.

Abstract

We have previously shown that H2^b mice with B10 or BALB genetic backgrounds have higher basal levels of IgG2a than H2^k and H2^d congenic strains and, hence, have low IgG1/IgG2a ratios, which is consistent with a T1 cytokine milieu. The phenotypic marker of the high IgG2a levels, denoted immunoglobulin isotype-1 (Igis1) was provisionally mapped telomeric of IE using MHC recombinant mice. In addition, data from B10.A(2R), B10.A(1R) and B10.A(18R) mice indicated that Igis1 may lie in a 27 kb region between G7b (Sm-X5) and G7c. In the present study we confirm that Igis1 is in the H2 region using BALB and B10 congenic F2 mice. H2^bb F2 mice had higher IgG2a levels than the H2^dd parental strains. H2^bd F1 and F2 mice on the B10 background produced IgG2a levels comparable with the H2^bb parental strain, indicating that the b allele was dominant. In contrast, the H2^bd F1 and F2 mice on the BALB background produced IgG2a levels between those of the H2^bb and H2^dd parental strains, indicating codominance of the b and d alleles. This suggests that a background gene influences regulation of IgG2a levels by Igis1. Non-obese diabetic (NOD) mice (K^dIA^g7IE^nu11D^b), which can develop type 1 diabetes, had higher levels of IgG2a than NOD-H2^d congenic mice. Thus, Igis1 affects isotype selection in the presence of non-MHC diabetes genes. As type 1 diabetes is associated with T1 responses, Igis1 may affect susceptibility to this condition.