McDonald A H, Byrd L G, Mainhart C R, Sopher J, Smith-Gill S J
Department of Pathology, Medical College of Wisconsin, Milwaukee 53226, U.S.A.
Mol Immunol. 1996 Oct;33(15):1183-96. doi: 10.1016/s0161-5890(96)00103-4.
Recently, a reduction in the incidence of pristane-induced plasmacytomas in BALB/cAnPt (BALB/c) mice that were kept in viral specific pathogen-free (SPF) conditions has been reported. Environmentally, these SPF-BALB/c mice differed from conventionally-housed (CON) mice only in viral exposure and diet (i.e. sterilization of mouse chow), since microbial colonization of the intestinal tract was seen to be equivalent. This report assessed the ability of SPF- and CON-BALB/c mice to respond to immunologic challenge with soluble antigen, i.e. hen egg white lyzosyme (HEL), as a means of evaluating differences in T and B cell function and, indirectly, evaluating the possible effects these differences might have on plasmacytoma development. When cultured in vitro for 5 days with HEL, HEL-primed lymph node cells (LNC) from SPF-BALB/c mice proliferated to a significantly lesser extent than HEL-primed CON-BALB/c LNC. Moreover, HEL-induced production of IFN-gamma and IL-5 was significantly lower in SPF LNC. Serum IgG1 levels were 10-fold lower in SPF-BALB/c mice with, or without prior immunization with HEL and were not reconstituted by repeated injections of HEL in adjuvant. Serum IgM levels of SPF- and CON-BALB/c mice were equivalent. This reduction in immune responses could not be attributed to a lack of colonization of secondary lymphoid organs, since flow cytometric analysis of LNC revealed no difference in the number of recoverable cells and the proportion of lymphocyte subsets (CD4+, CD8+ and CD45+ cells) obtained from SPF- and CON-BALB/c mice. However, only CON LNC were induced to increase surface expression of CD44 after antigenic or mitogenic stimulation in vitro. Antibody responsiveness to HEL, as evidenced by serum anti-HEL binding or splenic hybridoma studies, demonstrated higher levels of IgG1 antibodies in CON BALB/c mice than in SPF mice. However, a greater proportion of the SPF IgG1 antibodies present were specifically directed against HEL, so that specific activity was greater in SPF-BALB/c mice. Therefore, while SPF BALB/c mice have a more restricted response to HEL than CON-BALB/c mice, those antibodies that are produced are more specifically directed against HEL with very little apparent bystander/polyclonal activation of multireactive cells. Resistance to plasmacytomas in SPF-BALB/c mice, therefore, may stem from a reduced number of circulating memory T and B cells, which are capable of reacting and/or crossreacting with a chronic inflammatory stimulus.
最近，有报道称在处于病毒特定病原体-free（SPF）条件下饲养的BALB/cAnPt（BALB/c）小鼠中， pristane诱导的浆细胞瘤发病率有所降低。在环境方面，这些SPF-BALB/c小鼠与常规饲养（CON）小鼠的差异仅在于病毒暴露和饮食（即小鼠饲料灭菌），因为肠道的微生物定植情况被认为是相当的。本报告评估了SPF和CON-BALB/c小鼠对可溶性抗原（即鸡卵清溶菌酶，HEL）免疫挑战的反应能力，以此作为评估T细胞和B细胞功能差异的一种手段，并间接评估这些差异可能对浆细胞瘤发展产生的影响。当与HEL在体外培养5天时，来自SPF-BALB/c小鼠的经HEL致敏的淋巴结细胞（LNC）增殖程度明显低于经HEL致敏的CON-BALB/c LNC。此外，SPF LNC中HEL诱导的IFN-γ和IL-5产生明显更低。在有或没有预先用HEL免疫的情况下，SPF-BALB/c小鼠的血清IgG1水平低10倍，并且通过在佐剂中重复注射HEL也无法恢复。SPF和CON-BALB/c小鼠的血清IgM水平相当。免疫反应的这种降低不能归因于次级淋巴器官缺乏定植，因为对LNC的流式细胞术分析显示，从SPF和CON-BALB/c小鼠获得的可回收细胞数量以及淋巴细胞亚群（CD4 +、CD8 +和CD45 +细胞）的比例没有差异。然而，只有CON LNC在体外抗原或丝裂原刺激后被诱导增加CD44的表面表达。血清抗HEL结合或脾杂交瘤研究证明，CON BALB/c小鼠对抗HEL的抗体反应性高于SPF小鼠。然而，SPF中存在的IgG1抗体中更大比例是特异性针对HEL的，因此SPF-BALB/c小鼠的特异性活性更高。因此，虽然SPF BALB/c小鼠对HEL的反应比CON-BALB/c小鼠更受限，但产生的那些抗体更特异性地针对HEL，多反应性细胞的旁观者/多克隆激活很少。因此，SPF-BALB/c小鼠对浆细胞瘤的抗性可能源于循环记忆T细胞和B细胞数量的减少，这些细胞能够与慢性炎症刺激发生反应和/或交叉反应。
