Ridderstad A, Tarlinton D M
The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
J Immunol. 1998 May 15;160(10):4688-95.
In this report, we detail changes in the expression of CD38 on murine B cells during the course of a T cell-dependent immune response. CD38 is expressed on all naive B cells but is down-regulated on isotype-switched B cells from both the germinal centers (GCs) and the foci of Ab-forming cells which arise during the first weeks of the response. The down-regulation on GC B cells, however, is reversible since Ag-specific IgG1 B cells with high levels of CD38 are apparent by 2 wk postimmunization. These cells have characteristics that resemble recirculating memory B cells, in that they are small and bind low levels of peanut agglutinin. Such characteristics indicate that the restoration of CD38 levels is coincidental with the transition from GC to memory B cell. Using this observation, we plotted the development of the memory population and the demise of the GC reaction as a function of time after immunization. Our results indicate that the GC reaction ceases gradually over many weeks rather than suddenly, which corresponds with the formation of the memory B cell population. Furthermore, by segregating memory B cells and GC B cells, it was possible to assess the in vitro survival characteristics of each compared with naive B cells. These experiments demonstrated that memory B cell survival in vitro was comparable with naive B cell survival but less than the survival seen for bcl-2-transgenic B cells, whereas GC B cell survival, as expected, was very poor. Hence, by resolving murine Ag-specific memory B cells and GC B cells, we have been able to quantify the development of the memory B cell population.
在本报告中,我们详细阐述了在T细胞依赖性免疫反应过程中,小鼠B细胞上CD38表达的变化。CD38在所有未成熟B细胞上均有表达,但在生发中心(GCs)以及在反应最初几周出现的抗体形成细胞灶中的同种型转换B细胞上表达下调。然而,GC B细胞上的这种下调是可逆的,因为在免疫后2周时,高水平表达CD38的抗原特异性IgG1 B细胞明显可见。这些细胞具有类似于循环记忆B细胞的特征,即它们体积小且与低水平的花生凝集素结合。这些特征表明CD38水平的恢复与从GC B细胞向记忆B细胞的转变是同时发生的。利用这一观察结果,我们绘制了记忆细胞群体的发育以及GC反应的消亡随免疫后时间的变化曲线。我们的结果表明,GC反应是在数周内逐渐停止的,而不是突然停止,这与记忆B细胞群体的形成相对应。此外,通过分离记忆B细胞和GC B细胞,有可能评估与未成熟B细胞相比,每种细胞在体外的存活特性。这些实验表明,记忆B细胞在体外的存活与未成熟B细胞的存活相当,但低于bcl-2转基因B细胞的存活,而正如预期的那样,GC B细胞的存活非常差。因此,通过分辨小鼠抗原特异性记忆B细胞和GC B细胞,我们得以量化记忆B细胞群体的发育情况。