Kilchherr E, Mandak V, Wagner K, Heusser C H
Ciba-Geigy Limited, Basel, Switzerland.
Cell Immunol. 1993 Oct 15;151(2):241-56. doi: 10.1006/cimm.1993.1235.
The human IgE response was investigated in hu-PBL-SCID mice created by ip injection of human PBL into C.B.17 scid/scid (scid) mice. With 30-100 x 10(6) PBL/mouse, 80 to 90% of the animals responded with human IgE serum levels of 3-1000 ng/ml after 2 weeks. PBL from all donors analyzed (total number > 20) responded with IgE production. The half-lives of human IgE, IgM, and IgG in scid mice were determined to test the possibility of a passive transfer of the immunoglobulins in contrast to de novo synthesis. The values found were 88, 128, and 126 hr, respectively. In general, immunoglobulin production of all isotypes continuously increased over a period of 7-9 weeks after PBL injection, indicating de novo synthesis had taken place. The kinetics of the IgE response exhibited two phases: An initial burst of IgE production occurred between Days 12 and 22. This burst reached levels of 25-70 ng/ml IgE. After a rapid decline to about 50% of the peak value there was a sustained, slow, increase of IgE production for several weeks, excluding a passive transfer for IgE. About half of the donors lacked the initial burst of IgE production and only exhibited a slowly rising IgE production that is indistinguishable from the slow phase of the former donor population. The levels reached in this second phase of IgE production were 20-40 ng/ml after 6-7 weeks. This kinetics may reflect the presence of two different B cell populations, of which only one is present in all donors. The initial IgE burst was only partially dependent on the presence of human IL-4, reflected by a partial inhibition of this response by a neutralizing monoclonal anti-IL-4 antibody. The IgE response in scid mice seems to consist therefore of an IL-4-independent and an IL-4-dependent part, indicating the response to be partially driven by preswitched B cells. Injection of exogenous recombinant human IL-4 (rhIL-4) was not suitable due to the short half-life of rhIL-4 in scid mice of 12 min. Attempts to supply a constant source of rhIL-4 by injection of IL-4-producing Chinese hamster ovary cells failed because of toxic effects produced by these cells. The human IgE production in the scid mice was suppressed by interferon-alpha (BD) to 60-80% compared to that of untreated mice. The suppression was not isotype specific, however, because production of IgG and IgM was inhibited to similar extents.(ABSTRACT TRUNCATED AT 400 WORDS)
通过将人外周血淋巴细胞（PBL）腹腔注射到C.B.17 scid/scid（scid）小鼠中构建人PBL - SCID小鼠，对人IgE反应进行了研究。每只小鼠注射30 - 100×10⁶个PBL，2周后，80%至90%的动物血清中人IgE水平达到3 - 1000 ng/ml。分析的所有供体（总数>20）的PBL均有IgE产生。测定了scid小鼠中人IgE、IgM和IgG的半衰期，以检验免疫球蛋白被动转移而非从头合成的可能性。所得到的值分别为88、128和126小时。一般来说，在注射PBL后的7 - 9周内，所有同种型的免疫球蛋白产生持续增加，表明发生了从头合成。IgE反应的动力学表现为两个阶段：在第12天至22天之间出现IgE产生的初始爆发。该爆发达到25 - 70 ng/ml IgE的水平。在迅速下降至峰值的约50%后，IgE产生持续缓慢增加数周，排除了IgE的被动转移。约一半的供体缺乏IgE产生的初始爆发，仅表现出缓慢上升的IgE产生，这与前一供体群体的缓慢阶段无法区分。在IgE产生的第二阶段，6 - 7周后达到的水平为20 - 40 ng/ml。这种动力学可能反映了两种不同B细胞群体的存在，其中只有一种存在于所有供体中。初始IgE爆发仅部分依赖于人IL - 4的存在，这通过中和性抗IL - 4单克隆抗体对该反应的部分抑制得以体现。因此，scid小鼠中的IgE反应似乎由不依赖IL - 4和依赖IL - 4的部分组成，表明该反应部分由预转换的B细胞驱动。由于重组人IL - 4（rhIL - 4）在scid小鼠中的半衰期仅为12分钟，注射外源性rhIL - 4并不合适。通过注射产生IL - 4的中国仓鼠卵巢细胞来提供rhIL - 4恒定来源的尝试失败了，因为这些细胞产生了毒性作用。与未处理的小鼠相比，干扰素 - α（BD）将scid小鼠中的人IgE产生抑制至60% - 80%。然而，这种抑制并非同种型特异性的，因为IgG和IgM的产生也受到了类似程度的抑制。（摘要截短至400字）
