T cell-independent responses to an Ir gene-controlled antigen. I. Characteristics of the immune response to insulin complexed to Brucella abortus.

Immune responses by mice to heterologous insulins are controlled by H-2-linked Ir genes. Antibody responses to insulin are T cell dependent (TD), and nonresponder mice fail to make detectable insulin-specific antibodies. To further analyze the role of T cells in regulation of immune responses to insulin, we have developed a method for induction of insulin-specific B cells in the relative absence of T cells. Insulin has been chemically coupled to the T cell-independent (TI) organism Brucella abortus (insulin-BA). Studies reported here demonstrate that in terms of kinetics of responses, isotype expression, and induction of responses in X-linked immunodeficient mice, insulin-BA behaves as a typical type-1 TI antigen. Despite these characteristic features, T cells appear to augment the response to insulin-BA. More importantly, insulin-BA stimulates IgM and IgG anti-insulin antibodies in all strains tested regardless of whether the mice were responders or nonresponders to the particular insulin tested. Thus insulin-BA should be a useful antigen for dissecting the cell interactions required for development of insulin-specific immunity.