HayGlass K T, Naides S J, Benacerraf B, Sy M S
Harvard Medical School, Department of Pathology, Boston, MA 02115.
J Mol Cell Immunol. 1985;2(2):107-17.
A role for Igh linked genes and the idiotypes they encode has been implicated in the activity of a variety of T cell subpopulations. Idiotype restricted T cell function has been observed for helper and suppressor cell populations. The finding that T cell receptor genes are distinct from B cell receptor (Igh) genes strongly argues against a direct role for immunoglobulin genes in the determination of the T cell repertoire. Nevertheless, idiotypic Ig determinants may play an indirect role in influencing the ultimate composition of the T cell repertoire. One approach to this question involves evaluation of T cell activity upon development in an immunoglobulin deficient environment. The availability of antigens which elicit T cell and antibody responses characterized by the expression of dominant crossreactive idiotypes under the control of Igh genes provides an ideal approach to investigate the basis for the expression of Igh-like structures on T cells and the concomitant functional genetic restrictions they determine. Thus, we have prepared B cell deficient mice by continuous treatment, beginning at birth, with rabbit anti-mouse IgM. The network which comprises the suppressor T cell response to azobenzenearsonate (ABA) was then examined in normal and anti-mu treated mice to assess what role, if any, immunoglobulin encoded determinants play in influencing the composition of the peripheral T cell pool. The results clearly demonstrate that the absence of Ig+ B cells leads to major alterations in the composition of the T cell repertoire. Anti-mu treated, but not normal rabbit Ig treated, mice produce TsF1 which fails to suppress cytotoxic T lymphocyte or helper T cell responses of normal syngeneic mice, yet efficiently suppresses those of syngeneic anti-mu treated recipients. Reciprocally, normal TsF1, though suppressive in normal Igh-1 syngeneic recipients, fails to affect the development of responses in anti-mu treated syngeneic mice. TsF1 obtained from anti-mu treated mice is antigen-specific. Testing of anti-mu TsF in a variety of normal or anti-mu treated recipients reveals no MHC restrictions. In marked contrast, anti-mu TsF reflects a novel pattern of Igh functional restrictions. The observed Igh restrictions were found to map to the idiotype encoding VH regions of the Ig heavy chain gene cluster (Igh-VH). The results demonstrate that T cell maturation in the virtual absence of environmental immunoglobulin can lead to profound changes in the composition of the T cell compartment. The means by which the absence of Ig encoded determinants leads to such changes is speculated upon.
免疫球蛋白重链（Igh）相关基因及其编码的独特型在多种T细胞亚群的活性中发挥了作用。在辅助性和抑制性细胞群体中均观察到独特型限制的T细胞功能。T细胞受体基因与B细胞受体（Igh）基因不同，这一发现有力地反驳了免疫球蛋白基因在决定T细胞库方面的直接作用。然而，独特型Ig决定簇可能在影响T细胞库的最终组成方面发挥间接作用。解决这个问题的一种方法是评估在免疫球蛋白缺陷环境中发育时的T细胞活性。在Igh基因控制下，能引发以显性交叉反应独特型表达为特征的T细胞和抗体反应的抗原的存在，为研究T细胞上Igh样结构的表达基础以及它们所决定的伴随功能遗传限制提供了理想的方法。因此，我们从出生开始用兔抗小鼠IgM持续处理制备了B细胞缺陷小鼠。然后在正常小鼠和抗μ处理的小鼠中检测由偶氮苯砷酸盐（ABA）引发的抑制性T细胞反应网络，以评估免疫球蛋白编码的决定簇在影响外周T细胞库组成方面是否发挥作用（如果有作用的话）。结果清楚地表明，Ig+B细胞的缺失会导致T细胞库组成的重大改变。抗μ处理而非正常兔Ig处理的小鼠产生的TsF1不能抑制同基因正常小鼠的细胞毒性T淋巴细胞或辅助性T细胞反应，但能有效抑制同基因抗μ处理受体的反应。相反，正常的TsF1虽然在正常Igh-1同基因受体中具有抑制作用，但不能影响抗μ处理的同基因小鼠中反应的发展。从抗μ处理的小鼠中获得的TsF1具有抗原特异性。在各种正常或抗μ处理的受体中检测抗μTsF，未发现MHC限制。与之形成鲜明对比的是，抗μTsF反映了一种新的Igh功能限制模式。观察到的Igh限制定位于编码Ig重链基因簇（Igh-VH）VH区的独特型。结果表明，在几乎没有环境免疫球蛋白的情况下T细胞成熟会导致T细胞区室组成的深刻变化。文中推测了Ig编码决定簇的缺失导致这种变化的方式。
