Minskoff S A, Matter K, Mellman I
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
J Immunol. 1998 Sep 1;161(5):2079-83.
Fc gamma receptors (Fc gamma RII) on B lymphocytes negatively regulate B cell receptor (BCR)-dependent activation upon cross-linking of the two receptors. The mechanism reflects the ability of the Fc gamma RII cytoplasmic tail to recruit specific phosphatases that inactivate elements of the BCR-signaling cascade. We now show that cross-linking also blocks the processing and presentation of BCR-bound Ag. This occurs because the Fc gamma RII isoform typically expressed by B cells (Fc gamma RII-B1) is incompetent for endocytosis. When cross-linked, Fc gamma RII-B1 acts as a dominant negative inhibitor of BCR endocytosis. In contrast, cross-linking of endocytosis-competent Fc gamma RII isoforms did not inhibit endocytosis or processing of BCR-bound Ag. Thus, Fc gamma RII-B1 acts not only to prevent B cell activation under conditions of Ab excess, but also to prevent clonotypic T cell activation by inhibiting the ability of B cells to generate specific MHC class II-bound TCR ligands.
B淋巴细胞上的Fcγ受体（FcγRII）在两种受体交联时对B细胞受体（BCR）依赖性激活起负调节作用。该机制反映了FcγRII细胞质尾巴募集特定磷酸酶的能力，这些磷酸酶会使BCR信号级联反应的元件失活。我们现在表明，交联还会阻断BCR结合抗原的加工和呈递。这是因为B细胞通常表达的FcγRII同种型（FcγRII-B1）不具备内吞作用能力。交联时，FcγRII-B1作为BCR内吞作用的显性负抑制剂发挥作用。相比之下，具有内吞作用能力的FcγRII同种型的交联不会抑制BCR结合抗原的内吞作用或加工。因此，FcγRII-B1不仅在抗体过量的情况下阻止B细胞激活，还通过抑制B细胞产生特定的与MHC II类结合的TCR配体的能力来阻止克隆型T细胞激活。
