Sigal N H, Pickard A R, Metcalf E S, Gearhart P J, Klinman N R
J Exp Med. 1977 Oct 1;146(4):933-48. doi: 10.1084/jem.146.4.933.
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.
TEPC 15(T15)克隆型是一种推测为种系抗体特异性的类型,直到约1周龄时才出现在新生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克隆型在无菌小鼠和常规饲养小鼠中出现的动力学相似;(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C57BL/6或BALB/c母亲饲养的CBFI新生小鼠在个体发育过程中与BALB/c新生小鼠同时获得T15克隆型;(c)出生后不久缺乏磷酸胆碱(PC)特异性B细胞也反映在新生儿中PC结合细胞的缺乏上;(d)在19天龄的胎儿肝脏或骨髓中直到出生后7天未发现PC特异性B细胞,这与它们在脾脏中的出现时间一致。这些发现,连同先前关于PC特异性脾B细胞在出生后第10天仍可耐受的报告,证实了T15克隆型出现的不变性和晚期性,并支持了获得B细胞库的高度有序、严格预定的机制。根据关于B细胞特异性个体发育的其他研究以及对抗体多样性产生机制的影响来讨论这些结果。