International Immunology, Vol. 4, No. 1, pp. 67-74,January 1992
© 1992 Japanese Society for Immunology
Self-limited autoimmune disease related to transient donor B cell activation in mice neonatally injected with semi-allogeneic F1 cells
Immunology, Hospital‘Marqués de Valdecilla’, University of Cantabna Santander, Spain
1 Rheumatology, Hospital‘Marqués de Valdecilla’, University of Cantabna Santander, Spain
2 Pathology Units, Hospital‘Marqués de Valdecilla’, University of Cantabna Santander, Spain
3 The Basel Institute for Immunology, Grenzacherstrasse 487 Basel 4058, Switzerland
Correspondence to: Correspondence to: J. Merino
BALB/c mice injected at birth with 108 semi-allogeneic (C57BL/6 x BALB.IgHb)F1 spleen cells develop a lupus-like syndrome in which autoantibodles bear exclusively the donor allotype. We have analyzed the evolution of donor B cell chimerism and the autoimmune manifestations during the first year of life in these mice. Anti-DNA, -histone, and -cardiolipln IgG antibodies as well as circulating immune complexes appeared in the second week of life, reached the highest values around the sixth week, and then progressively dropped to normal values after the sixth month in most mice. The kinetics of the evolution of the autoimmune manifestations, as well as the kinetics of serum donor Ig allotype, were parallel to the kinetics of donor B cell chimerism, which was particularly prominent in the spleens in early weeks of life, and progressively decreased after remission of the autoimmune syndrome. Membrane-proliferative glomerulonephritls, which was followed as the more representative histological abnormality in this model, was particularly evident after 10 weeks of life, but disappeared by the end of the follow-up. Interestingly, when mice with a self-limited disease were re-injected with 108 F1 spleen cells i.v., a flare in the serologlcal manifestations was observed. In these re-injected mice a predominance of anti-DNA, lgG1 antibodies bearing exclusively the donor allotype was also observed, as in the early weeks of life. These results emphasize the central role of donor B cell chimerism in the development and in the self-limitation of the autoimmune disease in parental mice neonatally injected with F1 cells and Indicate that the capacity to react with F1 cells, to generate a renewed burst of symptoms, persists in these mice after the disappearance of autoimmune findings.
Keywords: neonatal tolerance, lupus-like syndrome, allogeneic interactions
Received 27 March 1991, accepted 1 August 1991.
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