Morris S C, Cheek R L, Cohen P L, Eisenberg R A
Department of Microbiology/Immunology, University of North Carolina, Chapel Hill 27599.
J Immunol. 1990 Feb 1;144(3):916-22.
A chronic graft-vs-host (GVH) reaction induced in nonautoimmune mice by the transfer of Ia-incompatible spleen cells results in a syndrome that closely resembles SLE in the spectrum of autoantibodies and immunopathology. We have utilized Ia- and Igh-congenic strains to study the immunoregulation of autoantibody-producing B cells in this model. We have found that the autoantibodies are produced almost entirely by the host B cells. The transferred donor B cells contributed neither to the autoimmune response nor to the total serum Ig, with rare exceptions. The donor cell population did, however, exert an Igh allotype-specific immunoregulatory effect on the host B cells. For example, in allotype-heterozygous recipients, the autoantibodies were preferentially made by those host cells that expressed the donor allotype, whereas those host B cells that expressed nondonor allotype were relatively suppressed. In allotype-homozygous recipients, the donor cells frequently suppressed the host IgG2a allotype completely. This suppression sometimes prevented the IgG antichromatin response, although in other cases the response occurred with the use of a different isotype. In a final set of experiments, a chronic GVH reaction was induced in which both the donors and the recipients were Igh allotype heterozygous and yet differed at Ia. In this case, no donor influence on allotype should be expected; yet the IgG2a autoantibodies were clearly skewed toward the b allotype. These results show that host B cells play a unique role in the GVH autoimmune syndrome. In addition, they are immunoregulated in allotype-specific manners, some of which presumably involve interaction with donor T cells.
通过转移Ia不相容的脾细胞在非自身免疫小鼠中诱导的慢性移植物抗宿主（GVH）反应会导致一种综合征，该综合征在自身抗体谱和免疫病理学方面与系统性红斑狼疮（SLE）极为相似。我们利用Ia和Igh同基因品系来研究该模型中产生自身抗体的B细胞的免疫调节。我们发现自身抗体几乎完全由宿主B细胞产生。转移的供体B细胞对自身免疫反应和总血清Ig均无贡献，仅有罕见例外。然而，供体细胞群体确实对宿主B细胞发挥了Igh同种异型特异性免疫调节作用。例如，在同种异型杂合受体中，自身抗体优先由那些表达供体同种异型的宿主细胞产生，而那些表达非供体同种异型的宿主B细胞则受到相对抑制。在同种异型纯合受体中，供体细胞常常完全抑制宿主IgG2a同种异型。这种抑制有时会阻止IgG抗染色质反应，尽管在其他情况下会使用不同的同种型发生反应。在最后一组实验中，诱导了一种慢性GVH反应，其中供体和受体均为Igh同种异型杂合，但在Ia方面存在差异。在这种情况下，不应预期供体对同种异型有影响；然而，IgG2a自身抗体明显偏向b同种异型。这些结果表明宿主B细胞在GVH自身免疫综合征中发挥独特作用。此外，它们以同种异型特异性方式受到免疫调节，其中一些可能涉及与供体T细胞的相互作用。
