Abstract
The New Zealand obese (NZO) mouse strain shares with
the related New Zealand black (NZB) strain a number of
immunophenotypic traits. Among these is a high proportion
of B-1 B lymphocytes, a subset associated with autoantibody
production. Approximately 50% of NZO/HlLt
males develop a chronic insulin-resistant type 2 diabetes
syndrome associated with 2 unusual features: the presence
of B lymphocyte–enriched peri-insular infiltrates and
the development of anti-insulin receptor autoantibodies
(AIRAs). To establish the potential pathogenic contributions
ofBlymphocytes and AIRAs in this model, a disrupted immunoglobulin heavy chain gene (Igh-6) congenic on the
NZB/BlJ background was backcrossed 4 generations into
the NZO/HlLt background and was then intercrossed to
produce mice that initially segregated for wild-type versus
the mutant Igh-6 allele and thus permitted comparison
of syndrome development. A new flow cytometric assay
(AIRA binding to transfected Chinese hamster ovary
cells stably expressing mouse insulin receptor) showed IgM
and IgG subclass AIRAs in serum from Igh-6 intact males,
but not in