Expression and regulation of a recurrent anti-erythrocyte autoantibody idiotype in spleen cells from neonatal and adult BALB/c mice.
BALB/c spleen cells depleted of CD8+ T cells generate an autoantibody response to mouse RBC (MRBC) when cultured 5 days in the presence of syngeneic RBC. More than 80% of the cells secreting anti-MRBC antibody are blocked by an antiidiotypic mAb that recognizes the G8 Id. This G8 Id was originally identified in an autoimmune NZB mouse derived anti-MRBC mAb and later characterized as a dominant Id in NZB anti-MRBC autoantibodies. Furthermore, the CD8+ regulatory T cells that control this autoimmune response in BALB/c mice are specifically eliminated by cytotoxic treatment with the G8 mAb + C, suggesting that the regulatory cells recognize the G8 Id. Spleen cells from neonatal BALB/c mice, which lack those regulatory cells can generate an in vitro antibody response to MRBC without depletion of CD8+ cells. More than 80% of these AFC were also found to express the G8 Id. We propose that Id determinants on autoantibodies that are produced neonatally induce Id-specific regulatory cells that maintain peripheral tolerance to self-RBC throughout the life of normal animals.
Miller
R D
RD
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107.
Caulfield
M J
MJ
Calkins
C E
CE
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis*; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D006239:Haplotypes; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007130:Immunoglobulin Idiotypes / Q000032:analysis*; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology*
D001323:Autoantibodies; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes