Mozes E, Shearer G M
J Exp Med. 1971 Jul 1;134(1):141-61. doi: 10.1084/jem.134.1.141.
Previous cellular studies on the genetic regulation of immunological responsiveness for two immunopotent regions within the branched chain synthetic polypeptide (Phe, G)-Pro--L demonstrated a direct correlation between the number of detectable immunocompetent splenic precursor cells and the response patterns of SJL, DBA/1, and F(1) mice (21). In order to establish the cellular origin(s) of the genetic defect, the present study first demonstrated that thymus and bone marrow cell cooperation was required for (Phe, G)- and Pro--L-specific immune responses. Secondly, limiting dilution experiments, in which several graded and limiting inocula of marrow cells were mixed with a non-limiting number of 10(8) thymocytes and injected into irradiated, syngeneic recipients, indicated that the low responsiveness of the SJL and DBA/1 strains to the (Phe, G) and Pro--L specificities, respectively, could be attributed to a reduced number of precursor cells found in bone marrow. About five times more marrow precursors were detected in SJL mice for Pro--L than for (Phe, G), whereas about five times as many precursor cells were estimated for (Phe, G) as for Pro--L in the DBA/1 strain. These differences are similar to those obtained using spleen cells from unimmunized SJL and DBA/1 donors (21), and indicate that these genetically determined variations in responsiveness can be accounted for by differences in the frequencies of monospecific populations of immunocompetent cells present in bone marrow. In contrast, limiting dilution transfers of thymocytes or thymus-derived cells with an excess of syngeneic marrow cells resulted in equally frequent (Phe, G) and Pro--L responses for both SJL ad DBA/1 strains. This finding in conjunction with the observation that the generation of (Phe, G)- and Pro--L-specific responses were associated in individual recipients injected with limiting inocula of thymocytes indicated that a single population of thymocytes was stimulated by (Phe,G)-Pro--L. Therefore, it is improbable that the thymic population of immunocompetent cells contributes to expression of these genetically controlled defects.
先前针对支链合成多肽（苯丙氨酸，甘氨酸）-脯氨酸-亮氨酸中两个免疫活性区域免疫反应性的遗传调控所进行的细胞研究表明，可检测到的免疫活性脾前体细胞数量与SJL、DBA/1和F(1)小鼠的反应模式之间存在直接关联（21）。为了确定遗传缺陷的细胞起源，本研究首先证明了胸腺和骨髓细胞协同作用是（苯丙氨酸，甘氨酸）-和脯氨酸-亮氨酸特异性免疫反应所必需的。其次，有限稀释实验中，将几个分级的有限接种量的骨髓细胞与数量不限的10(8)个胸腺细胞混合，并注射到经辐射的同基因受体中，结果表明SJL和DBA/1品系分别对（苯丙氨酸，甘氨酸）和脯氨酸-亮氨酸特异性反应的低反应性可归因于骨髓中前体细胞数量的减少。在SJL小鼠中，检测到的针对脯氨酸-亮氨酸的骨髓前体细胞数量比针对（苯丙氨酸，甘氨酸）的大约多五倍，而在DBA/1品系中，估计针对（苯丙氨酸，甘氨酸）的前体细胞数量是针对脯氨酸-亮氨酸的大约五倍。这些差异与从未免疫的SJL和DBA/1供体获取的脾细胞所得到的差异相似（21），并表明这些遗传决定的反应性差异可由骨髓中存在的单特异性免疫活性细胞群体频率差异来解释。相反，用过量的同基因骨髓细胞进行胸腺细胞或胸腺来源细胞的有限稀释转移，结果显示SJL和DBA/1品系对（苯丙氨酸，甘氨酸）和脯氨酸-亮氨酸的反应频率相同。这一发现与以下观察结果相结合，即在注射有限接种量胸腺细胞的个体受体中，（苯丙氨酸，甘氨酸）-和脯氨酸-亮氨酸特异性反应的产生是相关的，这表明单一群体的胸腺细胞受到（苯丙氨酸，甘氨酸）-脯氨酸-亮氨酸的刺激。因此，免疫活性细胞的胸腺群体不太可能导致这些遗传控制缺陷的表达。
