Ciavarra R P, Burgess D H
Department of Microbiology and Immunology, Eastern Virginia Medical School, Norfolk 23501.
Cell Immunol. 1988 Jun;114(1):27-40. doi: 10.1016/0008-8749(88)90252-3.
We have evaluated the efficacy of mitogen (LPS/DxSO4)-activated B cells (B lymphoblasts) to function as antigen-presenting cells (APC) for vesicular stomatitis virus (VSV). Our studies revealed that B lymphoblasts induced potent cytotoxic thymus (T)-derived lymphocyte (CTL) activity in VSV-immune splenic T cells depleted of adherent accessory cells. Dose-response curves indicated that B lymphoblasts were approximately 15-20 times more efficient APC than spleen cells for CTL induction against VSV. There was little evidence of reprocessing of viral antigens by the responder population because only CTL activity restricted to the parental haplotype of the B lymphoblast was generated following stimulation of VSV-immune F1 T cells. B lymphoblasts activated VSV-specific memory CTL which expressed the Lyt-1-23+, AsGM1+ phenotype without activating natural killer and/or lymphokine-activated killer cells. The ability of B lymphoblasts to function as efficient APC was not related to enhanced viral replication in these cells because potent VSV-specific proliferative and class I-restricted CTL responses were induced by B lymphoblasts infected with VSV rendered noninfectious by exposure to ultraviolet (uv) light. This indicates that activated B cells can efficiently process and present input virion protein. Purified splenic B cells that were not activated by mitogen stimulation did not function as APC for VSV even at high multiplicities of infection. The failure of B cells to function as APC for VSV was related to inefficient uptake of VSV and their inability to provide accessory cell signals required for T-cell proliferation; both these functions developed following mitogen stimulation. These data suggest that activated B cells may function as a potent APC population for virus independent of the specificity of their immunoglobulin antigen receptor.
我们评估了丝裂原(脂多糖/右旋糖酐硫酸酯)激活的B细胞(B淋巴母细胞)作为水疱性口炎病毒(VSV)抗原呈递细胞(APC)的功效。我们的研究表明,在去除黏附性辅助细胞的VSV免疫脾T细胞中,B淋巴母细胞可诱导强大的细胞毒性胸腺来源淋巴细胞(CTL)活性。剂量反应曲线表明,对于诱导针对VSV的CTL,B淋巴母细胞作为APC的效率约为脾细胞的15 - 20倍。几乎没有证据表明应答群体对病毒抗原有再加工,因为在刺激VSV免疫的F1 T细胞后,仅产生了限于B淋巴母细胞亲本单倍型的CTL活性。B淋巴母细胞激活了VSV特异性记忆CTL,其表达Lyt-1-23 +、AsGM1 +表型,而未激活自然杀伤细胞和/或淋巴因子激活的杀伤细胞。B淋巴母细胞作为高效APC发挥作用的能力与这些细胞中病毒复制增强无关,因为被紫外线(uv)照射使其失去感染性的VSV感染的B淋巴母细胞可诱导强大的VSV特异性增殖和I类限制性CTL反应。这表明活化的B细胞可以有效地加工和呈递输入的病毒粒子蛋白。未被丝裂原刺激激活的纯化脾B细胞即使在高感染复数下也不能作为VSV的APC发挥作用。B细胞不能作为VSV的APC发挥作用与VSV摄取效率低下以及它们无法提供T细胞增殖所需的辅助细胞信号有关;这两种功能在丝裂原刺激后才发展。这些数据表明,活化的B细胞可能作为一种强大的病毒APC群体发挥作用,而与其免疫球蛋白抗原受体的特异性无关。