Expression of phosphorylcholine-specific B cells during murine development

Expression of phosphorylcholine-specific B cells during murine development
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小鼠发育过程中磷酸胆碱特异性 B 细胞的表达

DOI:
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发表时间:
1977
影响因子:
15.3
通讯作者:
N. Klinman
N. Klinman
中科院分区:
医学1区
文献类型:
--
作者:
N. Sigal;A. Pickard;E. Metcalf;P. Gearhart;N. Klinman

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TEPC 15(T15)克隆型是一种特异性的脓毒症生殖系抗体,直到大约1周龄才出现在新生儿B细胞库中。本报告通过以下证明扩展了这一观察结果:(a)T15克隆型在无菌和常规饲养小鼠中的出现遵循相似的动力学;(B)母体影响和遗传背景在T15克隆型的发育中起次要作用,因为由C57 BL/6或BALB/c母体饲养的CBFI新生儿在个体发育中与BALB/c新生儿同时获得T15克隆型;(c)出生后不久磷酸胆碱(PC)特异性B细胞的缺乏也反映在新生儿中PC结合细胞的缺乏上;和(d)在19天的胎儿肝脏或出生后7天的骨髓中没有发现PC特异性B细胞,这与它们在脾脏中的出现一致。这些发现,沿着先前的报道,即PC特异性脾B细胞迟至出生后第10天是可耐受的,证实了T15克隆型的不变的晚期出现,并支持了获得B细胞库的高度有序的、严格预定的机制。结果进行了讨论,在光的B细胞特异性的个体发育的其他研究,并在抗体的多样性产生的机制的影响。
The TEPC 15 (T15) clonotype, a putatively germline antibody specificity, does not appear in the neonatal B-cell repertoire until approximately 1 wk of age. This report extends this observation by the demonstration that (a) the T15 clonotype follows similar kinetics of appearance in germfree as well as conventionally-reared mice; (b) maternal influences and genetic background play a minor role in the development of the T15 clonotype since CBFI neonates raised by C57BL/6 or BALB/c mothers acquire the T15 clonotype at the same time in ontogeny as BALB/c neonates; (c) the lack of phosphorylcholine (PC)-specific B cells shortly after birth is reflected in a dearth of PC-binding cells in the neonate as well; and (d) no PC-specifc B cells are found in 19-day fetal liver or in bone marrow until 7 days of life, coincident with their appearance in the spleen. These findings, along with a previous report that PC-specific splenic B cells are tolerizable as late as day 10 after birth, confirm the invariant, late occurrence of the T15 clonotype and support a highly- ordered, rigorously predetermined mechanism for the acquisition of the B- cell repertoire. The results are discussed in light of other studies on the ontogeny of B-cell specificity, and in terms of the implications on the mechanism by which antibody diversity is generated.