Fultz M J, Finkelman F D, Metcalf E S
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
Infect Immun. 1989 Feb;57(2):432-7. doi: 10.1128/iai.57.2.432-437.1989.
Using a modification of the splenic focus assay, we analyzed the Salmonella typhimurium-specific B-cell repertoire in salmonella-susceptible BALB/c mice. Although these mice normally succumbed to salmonella infection before antibody was produced, they appeared to have splenic S. typhimurium-specific B-cell precursors that could be activated to differentiate and secrete antibody in a manner which was quantitatively and qualitatively identical to that of salmonella-resistant mouse strains. We also analyzed the primary S. typhimurium-specific B-cell repertoire in BALB/c mice that had been chronically treated with antibodies to immunoglobulin D (IgD) and therefore had no surface IgD-positive B cells. Although the frequency of S. typhimurium-specific precursors in these mice was similar to that of control mice, there was an apparent alteration in the isotype distribution pattern in anti-IgD-treated mice. Control mice generated a significantly greater proportion of IgG-secreting clones than did anti-IgD-treated mice. In addition, a greater proportion of S. typhimurium-specific clones from control mice secreted IgG2 than secreted IgG1, and those clones that secreted IgG2 but not IgM, IgG3, or IgG1 were greater than 20-fold more common in control than in anti-IgD-treated mice. Finally, we analyzed the immune response of control and anti-IgD-treated mice to a live avirulent vaccine, S. typhimurium SL3235. Although both groups were protected after challenge with a live virulent S. typhimurium strain, only the control mice made serum antibodies to this vaccine. Taken together, these results show that (i) salmonella-susceptible BALB/c mice have S. typhimurium-specific B cells, (ii) the S. typhimurium-specific B cells in anti-IgD-treated mice may have a restricted capacity to switch heavy-chain classes, (iii) the similarity observed in the frequency of the S. typhimurium-specific precursors for these two groups of BALB/c mice is not reflected in the serum, and (iv) the failure of anti-IgD-treated mice to generate a serum antibody response to SL3235 in the face of complete protection suggests that this model may be used to study cell-mediated immune mechanisms in the apparent absence of humoral immunity.
我们采用改良的脾集落试验，分析了对沙门氏菌易感的BALB/c小鼠体内鼠伤寒沙门氏菌特异性B细胞库。尽管这些小鼠通常在产生抗体之前就死于沙门氏菌感染，但它们似乎拥有脾鼠伤寒沙门氏菌特异性B细胞前体，这些前体能够以与抗沙门氏菌小鼠品系在数量和质量上相同的方式被激活，从而分化并分泌抗体。我们还分析了长期用抗免疫球蛋白D（IgD）抗体处理因而没有表面IgD阳性B细胞的BALB/c小鼠体内的原发性鼠伤寒沙门氏菌特异性B细胞库。尽管这些小鼠体内鼠伤寒沙门氏菌特异性前体的频率与对照小鼠相似，但抗IgD处理的小鼠在同种型分布模式上有明显改变。对照小鼠产生分泌IgG的克隆比例明显高于抗IgD处理的小鼠。此外，对照小鼠中鼠伤寒沙门氏菌特异性克隆分泌IgG2的比例高于分泌IgG1的比例，且那些分泌IgG2但不分泌IgM、IgG3或IgG1的克隆在对照小鼠中比在抗IgD处理的小鼠中常见20倍以上。最后，我们分析了对照小鼠和抗IgD处理的小鼠对减毒活疫苗鼠伤寒沙门氏菌SL3235的免疫反应。尽管两组在用活的强毒鼠伤寒沙门氏菌菌株攻击后均受到保护，但只有对照小鼠产生了针对该疫苗的血清抗体。综上所述，这些结果表明：（i）对沙门氏菌易感的BALB/c小鼠拥有鼠伤寒沙门氏菌特异性B细胞；（ii）抗IgD处理的小鼠体内鼠伤寒沙门氏菌特异性B细胞在重链类别转换方面的能力可能受限；（iii）这两组BALB/c小鼠在鼠伤寒沙门氏菌特异性前体频率上观察到的相似性在血清中并未体现；（iv）抗IgD处理的小鼠在完全受到保护的情况下未能产生针对SLH3235的血清抗体反应，这表明该模型可用于在明显缺乏体液免疫的情况下研究细胞介导的免疫机制。
