Wagle N M, Faassen A E, Kim J H, Pierce S K
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208, USA.
J Immunol. 1999 Mar 1;162(5):2732-40.
The processing and presentation of Ag by Ag-specific B cells is highly efficient due to the dual function of the B cell Ag receptor (BCR) in both signaling for enhanced processing and endocytosing bound Ag. The BCR for IgG (FcgammaRIIB1) is a potent negative coreceptor of the BCR that blocks Ag-induced B cell proliferation. Here we investigate the influence of the FcgammaRIIB1 on BCR-mediated Ag processing and show that coligating the FcgammaRIIB1 and the BCR negatively regulates both BCR signaling for enhanced Ag processing and BCR-mediated Ag internalization. Treatment of splenic B cells with F(ab')2 anti-Ig significantly enhances APC function compared with the effect of whole anti-Ig; however, whole anti-Ig treatment is effective when binding to the FcgammaRIIB1 was blocked by a FcgammaRII-specific mAb. Processing and presentation of Ag covalently coupled to anti-Ig were significantly decreased compared with Ag coupled to F(ab')2anti-Ig; however, the processing of the two Ag-Ab conjugates was similar in cells that did not express FcgammaRIIB1 and in splenic B cells treated with a FcgammaRII-specific mAb to block Fc binding. Internalization of monovalent Ag by B cells was reduced in the presence of whole anti-Ig as compared with F(ab')2 anti-Ig, but the internalized Ag was correctly targeted to the class II peptide loading compartment. Taken together, these results indicate that the FcgammaRIIB1 is a negative regulator of the BCR-mediated Ag-processing function.
由于B细胞抗原受体（BCR）在增强加工信号传导和内吞结合抗原方面具有双重功能，因此抗原特异性B细胞对抗原的加工和呈递效率很高。IgG的BCR（FcγRIIB1）是BCR的一种有效的负性共受体，可阻断抗原诱导的B细胞增殖。在此，我们研究了FcγRIIB1对BCR介导的抗原加工的影响，并表明同时连接FcγRIIB1和BCR会对增强抗原加工的BCR信号传导和BCR介导的抗原内化均产生负向调节作用。与完整抗Ig的作用相比，用F（ab'）2抗Ig处理脾B细胞可显著增强抗原呈递细胞（APC）功能；然而，当与FcγRIIB1的结合被FcγRII特异性单克隆抗体阻断时，完整抗Ig处理是有效的。与偶联F（ab'）2抗Ig的抗原相比，与抗Ig共价偶联的抗原的加工和呈递显著降低；然而，在不表达FcγRIIB1的细胞以及用FcγRII特异性单克隆抗体处理以阻断Fc结合的脾B细胞中，两种抗原-抗体缀合物的加工情况相似。与F（ab'）2抗Ig相比，在存在完整抗Ig的情况下，B细胞对单价抗原的内化减少，但内化的抗原被正确靶向至II类肽装载区室。综上所述，这些结果表明FcγRIIB1是BCR介导的抗原加工功能的负性调节因子。
