International Immunology, Vol. 11, No. 7, 1035-1042,
July 1999
© 1999 Japanese Society for Immunology
Severe impairment of B cell function in lpr/lpr mice expressing transgenic Fas selectively on B cells
1 Department of Immunology and
2 Reproductive Engineering Section, Mitsubishi Kasei Institute of Life Sciences, Machida, Japan
3 Institute for Virus Research, Kyoto University, Kyoto, Japan
4 The Pharmaceutical Basic Research Laboratories, JT Inc., Yokohama, Japan
5 Department of Immunology, Kitasato University School of Medicine, Sagamihara, Kanagawa 228, Japan
Correspondence to: N. Shinohara, Department of Immunology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan
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.
Keywords: autoantibody, B cell, Fas, lpr
Transmitting editor: K. Okumura
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  N. Watanabe, K. Ikuta, S. Nisitani, T. Chiba, and T. Honjo Activation and Differentiation of Autoreactive B-1 Cells by Interleukin 10 Induce Autoimmune Hemolytic Anemia in Fas-deficient Antierythrocyte Immunoglobulin Transgenic Mice J. Exp. Med., July 1, 2002; 196(1): 141 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.C. GOODNOW, R. GLYNNE, D. MACK, B. WEINTRAUB, J. RATHMELL, J.I. HEALY, S. CHAUDHRY, L. MIOSGE, A. LOY, and L. WILSON Mechanisms of Self-tolerance and Autoimmunity: From Whole-animal Phenotypes to Molecular Pathways Cold Spring Harb Symp Quant Biol, January 1, 1999; 64(0): 313 - 322. [Abstract] [PDF]
|
|