Qi C F, Jessberger R, Torrey T A, Taddesse-Heath L, Ohta Y, Morse H C
Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0760, USA.
Mol Immunol. 1999 Oct-Nov;36(15-16):1043-53. doi: 10.1016/s0161-5890(99)00121-2.
Germinal centers (GC) are the sites of antigen-driven B cell switch recombination, V(D)J gene hypermutation, and selection to generate high-afinity CD38+ memory B cells. A marked expansion of GC associated with hypergammaglobulinemia followed by complete disruption of normal splenic architecture and a striking drop in immunoglobulin levels are prominent features of the murine retrovirus-induced immunodeficiency syndrome, MAIDS. B cell lymphomas are frequent in long-term infected mice. Normal GC formation is critically dependent on a number of genes including the transcription factor, Bcl6. Deregulated expression of BCL6 protein has been implicated in the development of human and mouse B cell lymphomas. Another nuclear protein, SWAP-70, has been identified as a subunit of the protein complex, SWAP, that recombines switch regions in vitro. To develop a fuller understanding of B cell biology in MAIDS, we examined the characteristics of BCL6, SWAP-70, CD38, and peanut agglutinin (PNA)-staining cells during the course of the disease. The levels of both nuclear proteins increased rapidly until 6-8 weeks after infection. During this time frame, BCL6 was expressed at highest levels in the usually rare CD4+ Thyl- T cell subset as well as in B cells. At later times. BCL6 levels dropped to undetectable levels while SWAP-70 levels continued to increase. Changes in the levels of either protein could not be ascribed to transcriptional regulation. PNA-reactive cells decreased in concert with BCL6 while CD38 staining increased with SWAP-70. These results demonstrate that progression of MAIDS results in the massive accumulation of B cells with the morphology of secretory cells that behave like post-GC cells for expression of BCL6 and CD38, and for PNA-staining but with abnormally high-level expression of SWAP-70.
生发中心（GC）是抗原驱动的B细胞类别转换重组、V（D）J基因超突变以及产生高亲和力CD38⁺记忆B细胞的选择位点。与高丙种球蛋白血症相关的生发中心显著扩张，随后正常脾脏结构完全破坏以及免疫球蛋白水平急剧下降，是鼠逆转录病毒诱导的免疫缺陷综合征MAIDS的突出特征。B细胞淋巴瘤在长期感染的小鼠中很常见。正常生发中心的形成严重依赖于许多基因，包括转录因子Bcl6。BCL6蛋白的失调表达与人类和小鼠B细胞淋巴瘤的发生有关。另一种核蛋白SWAP-70已被鉴定为蛋白复合物SWAP的一个亚基，该复合物在体外重组转换区。为了更全面地了解MAIDS中的B细胞生物学，我们在疾病过程中检查了BCL6、SWAP-70、CD38和花生凝集素（PNA）染色细胞的特征。两种核蛋白的水平在感染后6至8周迅速升高。在此期间，BCL6在通常罕见的CD4⁺Thy1⁻T细胞亚群以及B细胞中表达水平最高。在后期，BCL6水平降至检测不到的水平，而SWAP-70水平继续升高。两种蛋白水平的变化都不能归因于转录调控。PNA反应性细胞与BCL6一致减少，而CD38染色与SWAP-70一起增加。这些结果表明，MAIDS的进展导致具有分泌细胞形态的B细胞大量积累，这些细胞在BCL6和CD38表达以及PNA染色方面表现得像生发中心后细胞，但SWAP-70表达水平异常高。
