Flebbe L M, Braley-Mullen H
Cell Immunol. 1986 Apr 15;99(1):128-39. doi: 10.1016/0008-8749(86)90222-4.
The adjuvants SGP (a starch-acrylamide polymer) and Quil A (purified saponin) were shown to markedly augment antibody responses to T-independent (TI) antigens, suggesting that their adjuvant effects may be at least partially mediated through B cells. The ability of both adjuvants to augment primary responses to trinitrophenyl (TNP)-Ficoll (TI-2 antigen) in athymic nude mice further suggested these adjuvants affect B cells. SGP, however, did not induce a response to the T-dependent (TD) antigen dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH) in athymic nude mice, indicating it was unable to replace the requirement for T-helper cells for responses to TD antigens. Responses to TNP-lipopolysaccharide (LPS) were augmented by SGP in CBA/N X Balb/c immune defective (xid) mice. However, SGP was unable to induce a response to TNP-Ficoll in xid mice. The SGP and Quil A augmented responses to TNP-Ficoll were completely inhibited by the mitotic inhibitor, Velban, indicating that SGP and Quil A increased the plaque-forming cell (PFC) response primarily by stimulating cell proliferation, and not by recruitment of antigen-reactive cells. The effects of the adjuvants on secondary responses were investigated using adoptive transfer experiments. SGP and A1(OH)3 both increased the induction of hapten-specific memory B cells in mice primed with DNP-KLH. SGP, Quil A, and A1(OH)3 also increased priming of carrier specific T cells. Priming of memory B cells with DNP-KLH and either A1(OH)3 or SGP was prevented when T cells were depleted with anti-lymphocyte serum (ALS) at the time of antigen priming, indicating that the augmentation of memory B-cell priming by SGP and A1(OH)3 was dependent on the presence of functional T cells. SGP and Quil A were both unable to augment memory cell induction to the TI antigen, TNP-Ficoll, even though both adjuvants markedly augmented primary IgM and IgG responses to this antigen. Based on these results, it is suggested that SGP and Quil A can mediate their adjuvant effects primarily by a direct or indirect effect on B cells although the adjuvants may also affect T cells to some extent.
佐剂SGP(一种淀粉 - 丙烯酰胺聚合物)和Quil A(纯化的皂苷)已被证明能显著增强对非胸腺依赖性(TI)抗原的抗体反应,这表明它们的佐剂作用可能至少部分是通过B细胞介导的。这两种佐剂在无胸腺裸鼠中增强对三硝基苯基(TNP)- 菲可(TI - 2抗原)的初次反应的能力进一步表明这些佐剂会影响B细胞。然而,SGP在无胸腺裸鼠中并未诱导对胸腺依赖性(TD)抗原二硝基苯基 - 钥孔血蓝蛋白(DNP - KLH)的反应,这表明它无法替代对TD抗原反应时对辅助性T细胞的需求。在CBA/N×Balb/c免疫缺陷(xid)小鼠中,SGP增强了对TNP - 脂多糖(LPS)的反应。然而,SGP在xid小鼠中无法诱导对TNP - 菲可的反应。有丝分裂抑制剂长春花碱完全抑制了SGP和Quil A增强的对TNP - 菲可的反应,这表明SGP和Quil A主要通过刺激细胞增殖而非募集抗原反应性细胞来增加空斑形成细胞(PFC)反应。使用过继转移实验研究了佐剂对二次反应的影响。SGP和氢氧化铝(A1(OH)3)都增加了用DNP - KLH免疫的小鼠中半抗原特异性记忆B细胞的诱导。SGP、Quil A和A1(OH)3也增加了载体特异性T细胞的致敏。当在抗原致敏时用抗淋巴细胞血清(ALS)耗尽T细胞时,用DNP - KLH和A1(OH)3或SGP致敏记忆B细胞的过程被阻止,这表明SGP和A1(OH)3增强记忆B细胞致敏依赖于功能性T细胞的存在。尽管SGP和Quil A都显著增强了对TI抗原TNP - 菲可的初次IgM和IgG反应,但它们都无法增强对该抗原的记忆细胞诱导。基于这些结果,有人提出SGP和Quil A主要可通过对B细胞的直接或间接作用来介导其佐剂效应,尽管这些佐剂在一定程度上也可能影响T细胞。