Studies on the mode of action of TSBAb

甲状腺刺激阻断抗体（TSBAb）可阻断TSH对甲状腺的刺激作用，被认为是导致甲状腺功能减退的原因。TSBAb有两种类型，一种类型通过直接结合TSH受体（TSH结合抑制性免疫球蛋白（TBII）阳性阻断抗体）对TSH具有阻断作用，另一种类型具有阻断作用，但不影响TSH与其受体的结合（TBII阴性阻断抗体）。对TSBAb的作用方式进行了研究。TSBAb对甲状腺细胞膜的作用具有高TBII活性的TSBAb可显著阻断tsh刺激的猪甲状腺细胞（PTC） cAMP的产生。然而，TSBAb对猪离体甲状腺膜（PTM）中福斯克林、GTP γ S或NaF刺激的cAMP增加没有阻断作用。TSBAb活性被PTM吸收，但在某些情况下，这两种膜都吸收了TSBAb- igg中的TBII活性，但没有被豚鼠附睾脂肪膜吸收。这表明TSBAb可能通过TSH受体或甲状腺膜上的非TSH受体组分阻断TSH的作用，而不是通过受体后水平。实验兔中TSBAb的产生制备的抗PTM兔抗体显示TSBAb活性，而TBII活性为阴性。事实表明，这种类型的TSBAb可以针对甲状腺膜起源的任何抗原产生，除了TSH受体。蛋白酶消化TSBAb-IgG促甲状腺活性的表现TSBAb-IgG无促甲状腺活性，经蛋白酶消化转化为促甲状腺活性。促甲状腺活性位于Fab区，成分分数小得多。

The thyroid stimulation blocking antibody (TSBAb) which block the stimulatory effect of TSH on thyroid has been suggested as the causal factor of hypothyroidism.There are two types of TSBAb, one type has a blocking action on TSH by its direct binding to the TSH receptor [TSH binding inhibitory immunoblobulin (TBII) positive blocking antibody] and the other type has a blocking action without affecting TSH binding to its receptor (TBII negative blocking antibody). The study on mode of action of TSBAb was performed.1. The action of TSBAb on thyroid cell membraneThe TSBAb with high TBII activities significantly blocked TSH-stimulated cAMP production in porcine thyroid cells (PTC). However, there was no blocking action of TSBAb on the cAMP increase stimulated by forskolin, GTP gamma S,or NaF in isolated porcine thyroid membrane (PTM). The TSBAb activity was absorbed with PTM,but was not absorbed with guinea-pig epididymal fat membrane in some cases in spite of the absorption of the TBII activity in TSBAb-IgG by these two membranes. This suggests that TSBAb may block TSH action either via the TSH receptor or via a non-TSH receptor component of the thyroid membrane and not at a post receptor level.2. Production of TSBAb in experimental rabbitsThe produced antibody in rabbits against PTM showed the TSBAb activity in spite of negative TBII activity. The fact suggests that this type of TSBAb may be produced against any antigen of thyroid membrane origin except the TSH receptor.3.Appearence of thyroid stimulating activity from TSBAb-IgG by protease digestionThe innocent action (without thyroid stimulating activity) of TSBAb-IgG was converted to the thyroid stimulating activity by protease digestion. The thyroid stimulating activity located in Fab and the much smaller component fraction.