Sieckmann D G, Holmes K, Hornbeck P, Martin E, Guelde G, Bondada S, Longo D L, Kenny J J
Infectious Diseases Department, Naval Medical Research Institute, Bethesda, MD 20889-5607.
J Immunol. 1994 May 15;152(10):4873-83.
The transgenic (TG) mouse strain 207-4, carries mu a + kappa transgenes ligated to the anti-phosphocholine (PC) VH1 and V kappa 24 V region genes from the MOPC-167 myeloma. Although B cells from mice carrying these transgenes respond both in vivo and in vitro to thymus-dependent Ags, they failed to proliferate in response to soluble goat anti-mu Ab or other soluble anti-Ig reagents. On the other hand, B cells from the Sp6 mu kappa anti-trinitrophenyl TG mouse line proliferated normally after stimulation with soluble anti-mu. However, the 207-4 anti-PC transgene positive (TG+) splenic B cells proliferated when stimulated with anti-mu, anti-idiotype, anti-allotype, or PC-conjugated to Sepharose beads. TG+ B cells were also induced to proliferate when stimulated with anti-Lyb-2; thus, their defect may be restricted to signaling through sigM. The lack of response to soluble anti-mu could not be reversed by addition of IL-4, by removal of T cells, by addition of anti-FcR Ab, or by stimulation with F(ab')2 anti-mu. Thus, the failure to proliferate was not caused by active T cell suppression or FcR-mediated inhibition. In mixed cultures of TG+ and transgene negative (TG-) spleen cells, the TG- cells were able to proliferate normally to soluble anti-mu, indicating that suppressive factors were not involved in the unresponsiveness of the TG+ anti-PC-specific B cells. These studies suggest that B cells in the 207-4 anti-PC TG mice exhibit a defect in activation through their sIgM receptors, and this unresponsiveness may reflect a form of Ag-induced tolerance.
转基因（TG）小鼠品系207 - 4携带与来自MOPC - 167骨髓瘤的抗磷酸胆碱（PC）VH1和Vκ24 V区基因连接的μa + κ转基因。尽管携带这些转基因的小鼠的B细胞在体内和体外对胸腺依赖性抗原均有反应，但它们对可溶性山羊抗μ抗体或其他可溶性抗Ig试剂无增殖反应。另一方面，来自Sp6 μκ抗三硝基苯基TG小鼠品系的B细胞在用可溶性抗μ刺激后能正常增殖。然而，用抗μ、抗独特型、抗同种异型或与琼脂糖珠偶联的PC刺激时，207 - 4抗PC转基因阳性（TG +）脾B细胞会增殖。用抗Lyb - 2刺激时，TG + B细胞也会被诱导增殖；因此，它们的缺陷可能仅限于通过sigM进行信号传导。添加IL - 4、去除T细胞、添加抗FcR抗体或用F(ab')2抗μ刺激均不能逆转对可溶性抗μ的无反应性。因此，增殖失败不是由活性T细胞抑制或FcR介导的抑制引起的。在TG +和转基因阴性（TG -）脾细胞的混合培养物中，TG -细胞对可溶性抗μ能正常增殖，这表明抑制因子不参与TG +抗PC特异性B细胞的无反应性。这些研究表明，207 - 4抗PC TG小鼠中的B细胞通过其sIgM受体激活存在缺陷，这种无反应性可能反映了一种抗原诱导的耐受形式。
