Heyman B
Department of Genetics and Pathology, Uppsala University, Sweden.
Immunol Lett. 1999 May 3;68(1):41-5. doi: 10.1016/s0165-2478(99)00028-0.
IgG antibodies can negatively regulate antibody responses. When IgG anti-sheep erythrocytes (SRBC) is administered to an animal together with SRBC, the response against SRBC will frequently be less than 1% of the response in animals immunized with SRBC alone. The mechanism behind this phenomenon is not fully understood. It has been suggested that suppression is caused by masking of epitopes by IgG, thus preventing B cells from recognizing the antigen. Other possible explanations are that IgG/antigen complexes are eliminated via Fc-receptor dependent phagocytosis or that the complexes inhibit B cell activation by co-crosslinking the B cell receptor for antigen and the inhibitory Fc-receptor, FcgammaRIIB, expressed by B cells. Whereas the first mechanism would operate independently of the Fc-portion of IgG, the two latter would be Fc-dependent. In the literature data has been presented supporting both Fc-dependence and Fc-independence of suppression. It has recently been shown that IgG suppresses more than 90% of the antibody response in gene targeted mice lacking the known Fc-receptors for IgG and that F(ab')2 fragments as well as IgE are efficient suppressors. These findings strongly suggest that IgG is able to efficiently suppress antibody responses independently of the Fc-part and favor the model of epitope masking. Here, a way of interpreting available experimental data which can explain many of the discrepancies in the literature, is presented.
IgG抗体可对抗体应答产生负调控作用。当将IgG抗绵羊红细胞（SRBC）与SRBC一同给予动物时，针对SRBC的应答通常会低于仅用SRBC免疫的动物应答的1%。这种现象背后的机制尚未完全明确。有人提出，抑制作用是由IgG对表位的掩盖所致，从而阻止B细胞识别抗原。其他可能的解释是，IgG/抗原复合物通过Fc受体依赖性吞噬作用被清除，或者这些复合物通过使抗原的B细胞受体与B细胞表达的抑制性Fc受体FcγRIIB共同交联来抑制B细胞活化。第一种机制的作用不依赖于IgG的Fc部分，而后两种机制则依赖于Fc。文献中已呈现出支持抑制作用既依赖Fc又不依赖Fc的数据。最近有研究表明，在缺乏已知的IgG Fc受体的基因靶向小鼠中，IgG可抑制超过90%的抗体应答，并且F(ab')2片段以及IgE也是有效的抑制剂。这些发现强烈表明，IgG能够独立于Fc部分有效地抑制抗体应答，这支持了表位掩盖模型。在此，本文提出了一种解释现有实验数据的方法，该方法能够解释文献中的许多差异。
