Kishimoto S, Takahama T, Mizumachi H
J Immunol. 1976 Feb;116(2):294-300.
An in vitro anti-TNP response of the spleen cells from aged C57BL/6J mice showed approximately 4-fold less PFC than did that from young adult mice. Anti-theta serum-treated young spleen cells gave an anti-TNP response that was definitely greater than the response of the anti-theta serum-treated aged spleen cells in the presence of the exogenous activated thymus cells as helper cells. These results suggest that the deficits in B cells may be partly responsible for the imparied anti-TNP response of the aged spleen cells. To examine further the capacity of stem cells in the bone marrow to generate B cells responsible for anti-TNP response in the spleen, we injected i.v. 1.5 to 2.0 times 10(7) bone marrow cells from young or aged mice into lethally irradiated syngeneic recipients that had previously been thymectomized. Four to 6 weeks later, 10(7) spleen cells from the two groups of these recipient mice were immunized with TNP-SRBC in the presence of the exogenous activated thymus cells and assayed for anti-TNP PFC. The response of the aged marrow-derived B cells was approximately one-half of that of the young marrow-derived B cells. The avidity for TNP determinant of the antibodies produced by the PFC was determined by the plaque-inhibition technique. The avidity of the antibodies produced by the aged mice was approximately 33 times lower than that by the young mice. Anti-TNP response of the young spleen cells were markedly enhanced by the addition of LPS to the cultures, whereas no or little enhancement of the response was induced in the aged spleen cells even in the presence of high concentration of LPS. In contrast, DNA synthesis of both the young and aged spleen cells was comparably stimulated by 1 mug/ml and 10 mug/ml of LPS, however, it was rather less in the aged spleen cells at a concentration of 100 mug/ml. Mechanisms responsible for the changes in avidity and responsiveness to LPS with aging are discussed.
老年C57BL/6J小鼠脾细胞的体外抗TNP反应显示，其产生的溶血空斑形成细胞（PFC）数量比年轻成年小鼠的少约4倍。用抗θ血清处理的年轻脾细胞在有外源性活化胸腺细胞作为辅助细胞的情况下，其抗TNP反应明显大于用抗θ血清处理的老年脾细胞的反应。这些结果表明，B细胞的缺陷可能部分导致了老年脾细胞抗TNP反应受损。为了进一步研究骨髓中的干细胞产生负责脾中抗TNP反应的B细胞的能力，我们静脉注射1.5至2.0×10⁷个来自年轻或老年小鼠的骨髓细胞到先前已切除胸腺的同基因致死性照射受体小鼠体内。4至6周后，将这两组受体小鼠的10⁷个脾细胞在有外源性活化胸腺细胞的情况下用TNP - 绵羊红细胞（TNP - SRBC）免疫，并检测抗TNP PFC。老年骨髓来源的B细胞的反应约为年轻骨髓来源的B细胞反应的一半。通过噬斑抑制技术测定PFC产生的抗体对TNP决定簇的亲和力。老年小鼠产生的抗体的亲和力比年轻小鼠产生的抗体的亲和力低约33倍。向培养物中添加脂多糖（LPS）可显著增强年轻脾细胞的抗TNP反应，而即使在高浓度LPS存在的情况下，老年脾细胞的反应也没有或仅有轻微增强。相比之下，1μg/ml和10μg/ml的LPS对年轻和老年脾细胞的DNA合成均有类似的刺激作用，然而，在100μg/ml浓度下，老年脾细胞的DNA合成相对较少。本文讨论了衰老过程中亲和力和对LPS反应性变化的相关机制。
