Cancro M P, Sigal N H, Klinman N R
J Exp Med. 1978 Jan 1;147(1):1-12. doi: 10.1084/jem.147.1.1.
The primary anti-phosphorylcholine (PC) response in BALB/c, C57BL/6, and congenic and recombinant inbred strains of these parental types has been examined in the splenic focus system. The frequencies of PC-specific precursors were shown to vary among these strains from 2 to 20 precursors per 10(6) splenic B cells. The distribution of these frequencies suggests that elements closely linked to or within the major histocompatibility complex may play a role in the determination of this parameter, although additional experiments are necessary to adequately assess this possibility. Moreover, all strains tested, regardless of immunoglobulin allotype, expressed monoclonal antibodies indistinguishable from the TEPC 15 myeloma protein (T15) clonotype. Further, the frequency of this clonotype in a given strain did not appear related to allotype, since both high and low T15 frequencies were found among strains of either the BALB/c (a(1)) or C57BL/6 (a(2)) allotype. The examination of normal serum for the T15 idiotype, however, revealed that only mice of the BALB/c allotype (a(1)) expressed the T15 idiotype in detectable quantities. After immunization with Diplococcus pneumoniae, sera from mice of the a(1) allotype consistently contained large quantities of the T15 idiotype, whereas sera from mice of the a(2) allotype exhibited various degrees of cross-reactivity with anti-T15 antibody. These results suggest that: (a) the allotype of an individual, although closely related to serum levels of an idiotype, is unrelated to the proportion of the precursor population which expresses that idiotype and; (b) the serum expression of a given idiotype may reflect regulatory processes, which act either during or before antigenic stimulation, rather than the actual clonotype representation in the repertoire. These findings indicate that distinctions must be made between the expression of idiotypic determinants within precursor B-cell populations and elements which regulate the subsequent appearance of those idiotypes in serum antibodies.
在脾灶系统中检测了BALB/c、C57BL/6以及这些亲本类型的同类系和重组近交系对磷酸胆碱(PC)的主要应答。结果显示,这些品系中PC特异性前体细胞的频率有所不同,每10⁶个脾B细胞中有2至20个前体细胞。这些频率分布表明,与主要组织相容性复合体紧密连锁或位于其中的元件可能在该参数的决定中发挥作用,不过还需要进行额外实验来充分评估这种可能性。此外,所有测试品系,无论免疫球蛋白同种异型如何,都表达了与TEPC 15骨髓瘤蛋白(T15)克隆型无法区分的单克隆抗体。此外,给定品系中这种克隆型的频率似乎与同种异型无关,因为在BALB/c(a(1))或C57BL/6(a(2))同种异型的品系中都发现了高和低T15频率。然而,对正常血清中T15独特型的检测表明,只有BALB/c同种异型(a(1))的小鼠表达了可检测量的T15独特型。用肺炎双球菌免疫后,a(1)同种异型小鼠的血清始终含有大量的T15独特型,而a(2)同种异型小鼠的血清与抗T15抗体表现出不同程度的交叉反应。这些结果表明:(a)个体的同种异型虽然与独特型的血清水平密切相关,但与表达该独特型的前体细胞群体比例无关;(b)给定独特型的血清表达可能反映了在抗原刺激期间或之前起作用的调节过程,而不是库中实际的克隆型表现。这些发现表明,必须区分前体B细胞群体中独特型决定簇的表达与调节这些独特型随后在血清抗体中出现的元件。