Severe impairment of B cell function in lpr/lpr mice expressing transgenic Fas selectively on B cells

Transgenic Ipr/Ipr mice expressing functional Fas selectively on B cells were produced in an attempt to elucidate the role of Fas on B cells in the regulation of autoantibody production. The homozygous Ipr/Ipr mice carrying the transgene did not produce anti-double-stranded DNA antibodies throughout their lives, whereas the development of abnormal Ipr T cells (double negative, B220(+)) was not suppressed. Further analyses, however, revealed that the expression of the transgenic Fas on B cells of Ipr/Ipr homozygous mice resulted in severe impairment of the B cell function. The defect was characterized by a decrease in the number of mature peripheral B cells, a reduction in the serum Ig level and the total failure of B cells to mount antibody responses to stimulations of T-dependent as well as T-independent antigens, Such a defect was prominent only when the transgene was expressed on the Ipr/Ipr homozygous background. On the contrary, B cells of the transgenic Ipr/Ipr mice were shown to be capable of producing Ig when stimulated with anti-CD40 in the presence of IL-4 and IL-5, Furthermore, Ipr/Ipr T cells showed enhanced nonspecific cytolytic activity. These observations suggested that the observed B cell defect was probably attributable to the destruction of activated B cells expressing transgenic Fas by aggressive Ipr/Ipr T cells.