THE MECHANISM OF ANTIGENIC STIMULATION OF PRIMARY AND SECONDARY CLONAL PRECURSOR CELLS
THE MECHANISM OF ANTIGENIC STIMULATION OF PRIMARY AND SECONDARY CLONAL PRECURSOR CELLS
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原代和继代克隆前体细胞的抗原刺激机制
DOI：
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发表时间：
1972
影响因子：
15.3
通讯作者：
N. Klinman
中科院分区：
文献类型：
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作者：
N. Klinman
将细胞转移到载体免疫的辐照小鼠中，可以对来自免疫和非免疫小鼠的抗2,4-二硝基苯（DNP）抗体产生细胞的克隆前体进行体外刺激分析。结果表明：(a)载体特异性增强对原代前体细胞的刺激是必需的，并且增加了源自次级前体细胞的可检测病灶的大小和数量。(b)这种载体特异性增强在刺激高亲和力抗体产生细胞的前体时最为明显。(c)初级疫源地产生的抗体与次级疫源地产生的抗体一样，似乎是同质的。(d)免疫后4-8个月小鼠正常脾脏中克隆前体出现的频率为免疫后4-8个月小鼠脾脏中克隆前体出现的频率的38%，用可溶性抗原特异性抑制供体小鼠，可使正常脾脏中克隆前体的数量减少5倍。(e)与载体引物小鼠产生的一抗血清抗体一样，一抗单灶抗体的平均关联常数小于二抗或血清抗体的10倍。(f)初级单灶抗体的亲和力对刺激抗原浓度有轻微的依赖性；然而，与刺激相一致的最小阈值亲和性是明显的。(g)游离半抗原抑制初级前体细胞的抗原刺激的浓度远低于抑制次级前体细胞所需的浓度。这些结果被解释为表明(a)初级刺激，像次级刺激一样，是由抗原对一群细胞的选择性刺激引起的，这些细胞在其潜在的抗体产物中彼此不同，但每个细胞只有一种这样的产物；(b)原代细胞的抗原受体与抗原相互作用，好像它们是单价的，而次级细胞的受体则是多价的；(c)抗原刺激似乎既需要受体对结合抗原具有相对较高的亲和力，又需要受体通过这种抗原相互连接；因此，刺激被认为是由抗原-受体聚集在细胞表面的受体稳定引起的；(d) t细胞似乎在交联抗原和扩大受刺激克隆的大小方面都起作用。
Cell transfers to carrier-immunized irradiated mice have permitted an analysis of the in vitro stimulation of clonal precursors of anti-2,4-dinitrophenyl (DNP) antibody-producing cells derived from both immune and nonimmune mice. The results indicate that: (a) carrier-specific enhancement is obligatory for stimulation of primary precursor cells and increases both the size and number of detectable foci derived from secondary precursors. (b) This carrier-specific enhancement is most apparent in the stimulation of precursors of high-affinity antibody producer cells. (c) The antibody produced by primary foci, like that of secondary foci, appears homogeneous. (d) The frequency of clonal precursors in normal spleens is 38% that in spleens from mice 4–8 months after immunization, and the number of such precursors in normal spleens can be reduced fivefold by specific suppression of donor mice with soluble antigen. (e) The average of association constants of primary monofocal antibodies, like that of primary serum antibody produced in carrier-primed mice, is less than 10-fold lower than that of secondary clonal or serum antibody. (f) The affinity of primary monofocal antibodies shows a slight dependence on stimulating antigen concentration; however, a minimum threshold affinity consonant with stimulation is apparent. (g) Free hapten inhibits antigenic stimulation of primary precursor cells at a much lower concentration than is required for the inhibition of secondary precursors. These results are interpreted as indicating that (a) primary stimulation, like secondary stimulation, results from the selective stimulation by antigen of a population of cells differing from one another in their potential antibody product but each having only a single such product; (b) the antigen receptors of primary cells interact with antigen as if they are monovalent while receptors of secondary cells evidence multivalence; (c) antigenic stimulation appears to require both a relatively high affinity of receptors for bound antigen and an interlinking of receptors through such antigen; stimulation is thus seen as resulting from a stabilization of receptors within antigen-receptor aggregates to the cell surface; (d) T-cells appear to serve both in cross-linking antigens and in amplifying the size of stimulated clones.