Pulleyblank B M, Nakhooda A F, Letarte M, Falk J A
Department of Immunology, University of Toronto, Ontario, Canada.
Hum Immunol. 1988 Sep;23(1):5-21. doi: 10.1016/0198-8859(88)90013-4.
Seven purified IgG monoclonal antibodies reactive with different epitopes on DQw1, DR, HLA-A3 or p85 glycoprotein of human lymphocytes have each been shown to inhibit pokeweed mitogen (PWM)-induced IgG and IgM secretion in a dose-dependent manner. Binding of these antibodies to their target antigens was required for the suppression. Antibodies of IgG1, IgG2 alpha, and IgG2b subclasses were able to inhibit both IgG and IgM secretion in the PWM system. The mechanisms by which two of the monoclonal antibodies (MoAbs)-77.34, specific for the class II antigen DQw1, and GAP A3, specific for the class I antigen HLA-A3-caused inhibition--were analyzed. The suppressive effects of 77.34 and GAP A3 were maximal when added at the initiation of the culture period. No inhibition of IL-2 production or cellular proliferation was detected. Supernatants obtained from inhibited cultures were not themselves suppressive. The F(ab')2 fragments of either 77.34 or GAP A3 failed to influence PWM-Ig secretion, indicating that intact IgG molecules were required. This suggests that the observed inhibition might be mediated via Fc receptors. Together F(ab')2 fragments of either 77.34 or GAP A3 and a control IgG2a protein did not reconstitute the inhibitory effects of intact 77.34 or GAP A3. Suppression, therefore, required intact Fc portions on the same IgG molecules as those that bound to DQw1 or HLA-A3. These studies suggest that populations of IgG molecules that crosslink sufficient numbers of Fc receptors with other cell surface antigens on peripheral blood mononuclear cells (PBMs) during the early stages of B-cell activation can inhibit Ig secretion. Crosslinking of B-cell Fc receptors with SIg has been proposed by others to act as a negative signal for Ig production; our data raise the possibility that crosslinking of FcR with B-cell plasma membrane components other than SIg can also suppress Ig secretion.
七种纯化的IgG单克隆抗体可与人淋巴细胞上DQw1、DR、HLA - A3或p85糖蛋白的不同表位发生反应，且均已证明它们能以剂量依赖的方式抑制商陆有丝分裂原（PWM）诱导的IgG和IgM分泌。这种抑制作用需要这些抗体与其靶抗原结合。IgG1、IgG2α和IgG2b亚类的抗体能够抑制PWM系统中的IgG和IgM分泌。对两种单克隆抗体（MoAbs）——针对II类抗原DQw1的77.34和针对I类抗原HLA - A3的GAP A3——产生抑制作用的机制进行了分析。77.34和GAP A3在培养期开始时加入时抑制作用最大。未检测到对IL - 2产生或细胞增殖的抑制作用。从受抑制培养物中获得的上清液本身没有抑制作用。77.34或GAP A3的F(ab')2片段均未能影响PWM - Ig分泌，这表明完整的IgG分子是必需的。这表明观察到的抑制作用可能是通过Fc受体介导的。77.34或GAP A3的F(ab')2片段与对照IgG2a蛋白一起均不能重建完整的77.34或GAP A3的抑制作用。因此，抑制作用需要与结合到DQw1或HLA - A3的IgG分子相同的完整Fc部分。这些研究表明，在B细胞激活的早期阶段，能够使外周血单个核细胞（PBMs）上足够数量的Fc受体与其他细胞表面抗原交联的IgG分子群体可以抑制Ig分泌。其他人提出B细胞Fc受体与表面免疫球蛋白（SIg）交联可作为Ig产生的负信号；我们的数据增加了FcR与除SIg之外的B细胞质膜成分交联也能抑制Ig分泌的可能性。
