Williams T E, Nagarajan S, Selvaraj P, Zhu C
George W. Woodruff School of Mechanical Engineering and Georgia Tech/Emory Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332-0363, USA.
Biophys J. 2000 Oct;79(4):1867-75. doi: 10.1016/S0006-3495(00)76436-8.
Fc receptor-antibody interactions are key mechanisms through which antibody effector functions are mediated. Neutrophils coexpress two low-affinity Fcgamma receptors, CD16b (FcgammaRIIIb) and CD32a (FcgammaRIIa), possessing overlapping ligand binding specificities but distinct membrane anchor and signaling capacities. Using K562 cell transfectants as a model, the kinetics of both separate and concurrent binding of CD16b and CD32a to surface-bound IgG ligands were studied. CD16b bound human IgG with 2-3 times higher affinity than did CD32a (A(c)K(a) = 4.1 and 1.6 x 10(-7) microm(4), respectively) and both FcgammaRs had similar reverse kinetic rates (k(r) = 0.5 and 0.4 s(-1), respectively). Because CD16b is expressed on neutrophils at a 4-5 times higher density than CD32a, our results suggest that CD16b plays the dominant role in binding of neutrophils to immobilized IgG. The question of possible cross-regulation of binding affinity between CD16b and CD32a was investigated using our multispecies concurrent binding model (Zhu and Williams, Biophys. J. 79:1850-1857, 2000). Because the model assumes independent binding (no cooperation among different species), the excellent agreement between the model predictions and the experimental data suggests that, when coexpressed on K562 cells, these two FcgammaRs do not interact in a manner that alters the kinetic rates of either molecule.
Fc受体与抗体的相互作用是介导抗体效应功能的关键机制。中性粒细胞共表达两种低亲和力Fcγ受体，即CD16b（FcγRIIIb）和CD32a（FcγRIIa），它们具有重叠的配体结合特异性，但膜锚定和信号传导能力不同。以K562细胞转染体为模型，研究了CD16b和CD32a分别及同时与表面结合的IgG配体结合的动力学。CD16b与人IgG结合的亲和力比CD32a高2 - 3倍（结合常数分别为4.1和1.6×10⁻⁷ μM⁴），且两种Fcγ受体的逆向动力学速率相似（分别为0.5和0.4 s⁻¹）。由于CD16b在中性粒细胞上的表达密度比CD32a高4 - 5倍，我们的结果表明CD16b在中性粒细胞与固定化IgG的结合中起主导作用。利用我们的多物种同时结合模型（Zhu和Williams，《生物物理杂志》79:1850 - 1857，2000）研究了CD16b和CD32a之间结合亲和力可能的交叉调节问题。由于该模型假设独立结合（不同物种之间无协同作用），模型预测与实验数据之间的良好一致性表明，当在K562细胞上共表达时，这两种Fcγ受体不会以改变任一分子动力学速率的方式相互作用。
