Heyman Birgitta
Department of Medical Biochemistry and Microbiology, Uppsala University, (BMC), Uppsala, Sweden.
Immunol Rev. 2024 Nov;328(1):126-142. doi: 10.1111/imr.13377. Epub 2024 Aug 23.
Antibodies are able to up- or downregulate antibody responses to the antigen they bind. Two major mechanisms can be distinguished. Suppression is most likely caused by epitope masking and can be induced by all isotypes tested (IgG1, IgG2a, IgG2b, IgG3, IgM, and IgE). Enhancement is often caused by the redistribution of antigen in a favorable way, either for presentation to B cells via follicular dendritic cells (IgM and IgG3) or to CD4 T cells via dendritic cells (IgE, IgG1, IgG2a, and IgG2b). IgM and IgG3 complexes activate complement and are transported from the marginal zone to follicles by marginal zone B cells expressing complement receptors. IgE-antigen complexes are captured by CD23 B cells in the blood and transported to follicles, delivered to CD8α conventional dendritic cells, and presented to CD4 T cells. Enhancement of antibody responses by IgG1, IgG2a, and IgG2b in complex with proteins requires activating FcγRs. These immune complexes are captured by dendritic cells and presented to CD4 T cells, subsequently helping cognate B cells. Endogenous feedback regulation influences the response to booster doses of vaccines and passive administration of anti-RhD antibodies is used to prevent alloimmunization of RhD-negative women carrying RhD-positive fetuses.
抗体能够上调或下调针对其结合抗原的抗体反应。可区分出两种主要机制。抑制作用很可能是由表位掩盖引起的，并且可由所有测试的同种型（IgG1、IgG2a、IgG2b、IgG3、IgM和IgE）诱导。增强作用通常是由抗原以有利方式重新分布所致，要么是通过滤泡树突状细胞呈递给B细胞（IgM和IgG3），要么是通过树突状细胞呈递给CD4 T细胞（IgE、IgG1、IgG2a和IgG2b）。IgM和IgG3复合物激活补体，并由表达补体受体的边缘区B细胞从边缘区转运至滤泡。IgE-抗原复合物在血液中被CD23 B细胞捕获并转运至滤泡，传递给CD8α传统树突状细胞，并呈递给CD4 T细胞。与蛋白质结合的IgG1、IgG2a和IgG2b增强抗体反应需要激活FcγRs。这些免疫复合物被树突状细胞捕获并呈递给CD4 T细胞，随后辅助同源B细胞。内源性反馈调节影响对疫苗加强剂量的反应，被动给予抗RhD抗体用于预防携带RhD阳性胎儿的RhD阴性女性的同种免疫。
