Borriero L, Giorgetti C, Smith G, Landry D, Selsing E, Zhukovsky E, Press J L
Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02254-9110.
J Immunol. 1990 Jan 15;144(2):583-92.
Although there is a nonrandom usage of VH gene families by primary B cells early in ontogeny, at issue is whether the preferential rearrangement of 3' germ-line VH genes, e.g., VH7183 and VHQ52 family genes, influences the neonatal B cell repertoire that can be expressed in response to Ag. In order to address this issue, and to determine whether neonatal B cells can use the same germ-line VH and V kappa genes as adult B cells in their primary response, we have analyzed at the molecular level the neonatal antibody response to (T,G)-A-L and compared it with the adult primary response. Among the TGB5 Id+, GT+ antibodies, which dominate the neonatal response to (T,G)-A-L, two VH gene families were used: J558 (high frequency) and 36-60 (low frequency). The majority of Id+ neonatal hybridomas used the same germ-line VH gene (H10, from the VHJ558 family), but with enormous diversity in the D region, and one of two germ-line V kappa 1 genes (V kappa 1A, V kappa 1C). These are the same germ-line V-genes used by most primary adult Id+ hybridomas, and the frequency of expression of this germ-line V-gene combination appears equivalent in the neonatal and adult primary repertoires. Therefore, it is clear from this study that as early as day 5, neonatal B cells can use the same germ-line V-genes as adult primary B cells in their Ag-specific repertoire.
虽然在个体发育早期原代B细胞对VH基因家族存在非随机使用情况,但问题在于3'胚系VH基因(例如VH7183和VHQ52家族基因)的优先重排是否会影响可针对抗原表达的新生B细胞库。为了解决这个问题,并确定新生B细胞在其初次应答中是否能使用与成年B细胞相同的胚系VH和Vκ基因,我们在分子水平上分析了新生小鼠对(T,G)-A-L的抗体应答,并将其与成年小鼠的初次应答进行比较。在主导新生小鼠对(T,G)-A-L应答的TGB5 Id +、GT +抗体中,使用了两个VH基因家族:J558(高频)和36 - 60(低频)。大多数Id +新生杂交瘤使用相同的胚系VH基因(H10,来自VHJ558家族),但在D区域具有巨大的多样性,以及两个胚系Vκ1基因之一(Vκ1A、Vκ1C)。这些是大多数成年原代Id +杂交瘤使用的相同胚系V基因,并且这种胚系V基因组合的表达频率在新生小鼠和成年小鼠的初次库中似乎相当。因此,从这项研究可以清楚地看出,早在第5天,新生B细胞在其抗原特异性库中就能使用与成年原代B细胞相同的胚系V基因。