A common cellular abnormality of all murine strains prone to systemic lupus erythematosus (SLE) is an increased spontaneous polyclonal expansion of B cells. Our findings support the existence of this SLE-associated abnormality because the numbers of B lymphocytes secreting all the different IgG subclasses and IgM in spleens of all lupus-prone mice are elevated, compared to levels of normal splenic immunoglobulin-producing cells. We also report that 1) spontaneous polyclonal stimulation of immunoglobulin in autoimmune mice is preferential for subclass, and that the preferentially stimulated isotypes in each SLE strain consistently dominate both circulating and kidney-deposited immune complexes; 2) distinct patterns of isotype preference exist among the autoimmune strains determined by inherent B cell proliferative abnormalities or by B cell proliferation affected by thymus-derived lymphocytes; and 3) chronic administration of the TI B cell mitogen Lipid A in late-life SLE-prone mice induces an early-life glomerulonephritis with auto-antibodies of an isotype composition characteristic of those spontaneously produced by inherently abnormal B cells of early-life lupus mice.