Durandy A, De Saint Basile G, Lisowska-Grospierre B, Gauchat J F, Forveille M, Kroczek R A, Bonnefoy J Y, Fischer A
INSERM U 132, Necker Hospital for Sick Children, Paris, France.
J Immunol. 1995 Feb 15;154(4):1560-8.
IgG, IgA, and IgE production by newborn B cells is limited both in vivo and in vitro in various activation conditions, whereas IgM production is readily detectable. It has been suggested that the Ig heavy chain switch inability could be the consequence of T and B cell immaturity. As the interaction between CD40 (expressed on B cells) and its ligand CD40-L (expressed on activated T cells) triggers a key signal required for isotype switching, we studied the expression and function of these two components in normal fetuses, newborns, and infants, compared with adults. CD40-L expression was not inducible in 28 of 30 specimens of newborn cord-blood T cells following incubation with PMA and ionomycin, whereas activation markers such as CD69 were inducible. CD40-L expression was triggered by activation of T cells from infants > 3 wk of age. Surprisingly, T cells from 19- to 28-wk-old fetuses also expressed CD40-L following activation. CD40-L expression on newborn T lymphocytes was induced on T cell lines generated in the presence of PHA and maintained with IL-2 following further stimulation with PMA and ionomycin. CD40-L mRNA transcripts and intracytoplasmic protein expression following activation of newborn T cells were strongly decreased, leading to undetectable protein membrane detection. These results point to a possible transcriptional down-regulation of CD40-L expression by neonatal T lymphocytes. In addition, fetal and cord-blood B cells were poorly able to switch to IgG or IgA by stimulation with CD40 agonists (Ab or soluble CD40-L) in the presence of IL-4 or IL-10 as also detected with surface IgD+ adult B cells. Both phenomena could contribute to the neonatal Ig switch inability, although distinct underlying regulatory mechanisms are probably involved, as suggested by different in vivo time courses.
在各种激活条件下，新生B细胞产生IgG、IgA和IgE的能力在体内和体外均受到限制，而IgM的产生则很容易检测到。有人提出，Ig重链转换无能可能是T细胞和B细胞不成熟的结果。由于B细胞上表达的CD40与其配体CD40-L（活化T细胞上表达）之间的相互作用触发了同种型转换所需的关键信号，我们研究了这两种成分在正常胎儿、新生儿和婴儿中的表达及功能，并与成年人进行了比较。在用佛波酯（PMA）和离子霉素孵育后，30份新生儿脐带血T细胞标本中有28份的CD40-L表达无法被诱导，而诸如CD69等激活标志物是可诱导的。3周龄以上婴儿的T细胞激活可触发CD40-L表达。令人惊讶的是，19至28周龄胎儿的T细胞激活后也表达CD40-L。在PHA存在下产生并在用PMA和离子霉素进一步刺激后用IL-2维持的T细胞系上，可诱导新生儿T淋巴细胞上的CD40-L表达。新生儿T细胞激活后的CD40-L mRNA转录本和胞浆内蛋白表达大幅下降，导致无法检测到蛋白膜表达。这些结果表明新生儿T淋巴细胞可能对CD40-L表达进行转录下调。此外，与表面IgD⁺成人B细胞一样，胎儿和脐带血B细胞在IL-4或IL-10存在下用CD40激动剂（抗体或可溶性CD40-L）刺激后，向IgG或IgA转换能力较差。这两种现象可能都导致了新生儿Ig转换无能，尽管可能涉及不同的潜在调节机制，体内不同的时间进程表明了这一点。
