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. 1994 Jun;82(2):287–293.

Differences in non-MHC alloantigens promote tissue rejection but fail to mediate allogeneic co-operation and autoimmunity in mice neonatally injected with semi-allogeneic F1 B cells.

A Ramos 1, R Merino 1, J Merino 1
PMCID: PMC1414834  PMID: 7927500

Abstract

Mice injected at birth with semi-allogeneic lymphoid cells develop a lupus-like autoimmune syndrome in which donor B cells are polyclonally activated by host alloreactive CD4+ T cells, producing autoantibodies and immune complex-mediated glomerulonephritis. It has been demonstrated that the recognition of major histocompatibility complex (MHC) class II alloantigens triggers the development of a complete disease. But differences in either MHC class I molecules or Mls-1 antigens are not sufficient to induce production of autoantibodies. Here we have investigated whether differences in other non-MHC alloantigens could induce a similar autoimmune disease and whether the maternal environment could modulate the T-B allogeneic co-operation in this model. For this purpose (BALB/c x BC20)F1 hybrid females were backcrossed with BC20 males. R2 mice obtained in this backcross were neonatally injected with 10(8) (C57BL/6 x BALB.Igb)F1 spleen cells and the tolerance against maternal derived BALB/c alloantigens as well as the development of autoimmune manifestations were subsequently evaluated. In contrast to R2 mice injected at birth with (C57BL/6 x BALB.Igb)F1 cells, control R2 mice rejected skin grafts from BALB/c mice and B cells from (C57BL/6 x BALB.Igb)F1 mice, independently of their H-2 haplotype (H-2b/d or H-2b/b). Nevertheless, after neonatal injection of (C57BL/6 x BALB.Igb)F1 cells, none of 19 H-2b/d R2 injected mice presented autoimmune manifestations, in contrast with the typical autoimmune disease observed in all neonatally injected H-2b/b R2 mice (26 mice). These results support that the development of autoimmunity in this model depends exclusively upon differences in MHC class II alloantigens and that the relationship between mother and fetus, through the pregnancy or the breast suckling, is not sufficient to inhibit cytolytic and allo-helper responses against non-inherited maternal-derived alloantigens.

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Selected References

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