Lemke H, Lange H, Berek C
Biochemisches Institut der Medizinischen Fakultät, Christian-Albrechts-Universität, Kiel, Germany.
Eur J Immunol. 1994 Dec;24(12):3025-30. doi: 10.1002/eji.1830241216.
The development of the antibody repertoire in newborn mice is greatly influenced by idiotype network interactions. It has been demonstrated that anti-idiotypic antibodies either directly injected or transferred from the mother may alter the repertoire for life. For an elucidation of the underlying mechanisms we have analyzed the primary immune response to 2-phenyl-5-oxazolone (phOx) coupled to chicken serum albumin (CSA) in BALB/c mice after complete disappearance of maternal antibodies which originated from different stages of affinity maturation. Depending on the serum titers of the mothers after primary (1 degree mo), secondary (2 degrees mo) or tertiary (3 degrees mo) immunization, maternal anti-phOx IgG persisted in F1 mice for up to 9 months. In addition, F1 mice born to 2 degrees mo developed--even without immunization--an anti-phOx IgM titer which reached levels similar to an antigen-induced primary response. An enhancement of the early primary anti-phOx as well as anti-CSA response was seen in F1 mice born from 1 degree mo, whereas the response was delayed when born to 2 degrees mo and 3 degrees mo. The antibody titers in the latter group of mice remained at a lower level for 3 months. In contrast, mice of the F2 generation which received a smaller amount of the same collection of maternal antibodies as F1 mice from 3 degrees mo exhibited a quite different primary response: (i) They showed an earlier onset in their anti-CSA response. (ii) Whereas normally a plateau in antibody titer was reached by the 4th weak after immunization, in 55% of the F2 mice a prolonged increase of the anti-phOx and anti-CSA antibody titers was observed. At 12 weeks after antigenic challenge, titers reached plateau levels of 6 x 10(5) which were never before seen in a primary phOx or CSA response. Thus, depending on its own immunological experience, the maternal immune system induces a state of memory in the offspring which results in a faster and/or enhanced immune response in the F1 and F2 [corrected] generations.
新生小鼠抗体库的发育受到独特型网络相互作用的极大影响。已证明，直接注射或从母体转移的抗独特型抗体可能会终生改变抗体库。为了阐明潜在机制，我们分析了在源自亲和力成熟不同阶段的母体抗体完全消失后，BALB/c小鼠对与鸡血清白蛋白（CSA）偶联的2-苯基-5-恶唑酮（phOx）的初次免疫反应。根据母体在初次（1°月）、二次（2°月）或三次（3°月）免疫后的血清滴度，母体抗phOx IgG在F1小鼠中持续存在长达9个月。此外，由2°月出生的F1小鼠即使未经免疫也产生了抗phOx IgM滴度，其水平达到与抗原诱导的初次反应相似的水平。在由1°月出生的F1小鼠中，早期初次抗phOx以及抗CSA反应增强，而由2°月和3°月出生时反应延迟。后一组小鼠的抗体滴度在3个月内保持在较低水平。相比之下，F2代小鼠从3°月母体获得的相同抗体量较少，其初次反应却大不相同：（i）它们的抗CSA反应起始更早。（ii）通常在免疫后第4周抗体滴度达到平台期，而在55%的F2小鼠中，抗phOx和抗CSA抗体滴度持续升高。在抗原攻击后12周，滴度达到6×10⁵的平台期水平，这在初次phOx或CSA反应中从未见过。因此，根据其自身免疫经验，母体免疫系统在后代中诱导出一种记忆状态，导致F1和F2代产生更快和/或更强的免疫反应。
