Severe impairment of B cell function in lpr/lpr mice expressing transgenic Fas selectively on B cells.
Transgenic lpr/lpr 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 lpr/lpr mice carrying the transgene did not produce anti-double-stranded DNA antibodies throughout their lives, whereas the development of abnormal lpr T cells (double negative, B220(+)) was not suppressed. Further analyses, however, revealed that the expression of the transgenic Fas on B cells of lpr/lpr 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 lpr/lpr homozygous background. On the contrary, B cells of the transgenic lpr/lpr mice were shown to be capable of producing Ig when stimulated with anti-CD40 in the presence of IL-4 and IL-5. Furthermore, lpr/lpr T cells showed enhanced non-specific 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 lpr/lpr T cells.
Komano
H
H
Department of Immunology, Mitsubishi Kasei Institute of Life Sciences, Machida, Japan.
Ikegami
Y
Y
Yokoyama
M
M
Suzuki
R
R
Yonehara
S
S
Yamasaki
Y
Y
Shinohara
N
N
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000235:genetics* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018076:DNA, Complementary / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007136:Immunoglobulins / Q000096:biosynthesis / Q000097:blood; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019076:Transgenes / Q000276:immunology; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*
D001323:Autoantibodies; D018076:DNA, Complementary; D007136:Immunoglobulins; D019014:fas Receptor