Suppression of immunoglobulin class synthesis in mice. I. Effects of treatment with antibody to -chain.
Suppression of immunoglobulin class synthesis in mice. I. Effects of treatment with antibody to -chain.
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DOI：
10.1084/jem.135.2.277
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发表时间：
1972-02-01
期刊：
影响因子：
--
通讯作者：
Cooper MD
中科院分区：
文献类型：
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作者：
Lawton AR 3rd;Asofsky R;Hylton MB;Cooper MD
无菌BALB/c小鼠从出生起就用纯化的羊抗小鼠免疫球蛋白M抗体进行治疗。在8或13周龄时，处理的小鼠和接受等量的山羊γ球蛋白的对照小鼠被处死。与对照组相比，(A)小鼠脾和淋巴结中生发中心极少，(B)脾中合成IgM和IgG1的成熟浆细胞数量减少，肠道中几乎没有合成IgA的浆细胞，(C)脾中携带IgM、IgG1、IgG2和IgA类免疫球蛋白的B淋巴细胞数量显著减少，(D)脾体外培养合成IgM、IgG2和IgA减少，(E)血清IgM、IgG1、IgG2和IgA水平显著下降。经处理的动物在超免疫后未能产生铁蛋白抗体，并且缺乏针对绵羊红细胞的天然抗体。这些结果表明，最终致力于合成IgG1、IgG2和IgA免疫球蛋白的细胞来自分化早期表达IgM决定簇的细胞。这与浆细胞分化的两阶段模型是一致的。第一阶段是抗原非依赖性阶段，由单个干细胞的后代依次激活Cµ、Cγ和Cα基因，形成携带每一类膜结合识别抗体的B淋巴细胞。第二个阶段是抗原依赖阶段，形成成熟的浆细胞和记忆细胞。
Germfree BALB/c mice have been treated from birth with intraperitoneal injections of purified goat antibodies to mouse IgM. The treated mice, and controls which had received an equivalent amount of goat γ-globulin, were sacrificed at 8 or 13 wk of age. Compared to controls, mice given anti-µ (a) had very few germinal centers in spleen and lymph node, (b) had decreased numbers of mature plasma cells synthesizing IgM and IgG1 in spleen, and virtual absence of IgA-synthesizing plasma cells in the gut, (c) had greatly diminished numbers of B lymphocytes bearing membrane-bound immunoglobulins of the IgM, IgG1, IgG2, and IgA classes in spleen, (d) had reduced synthesis of IgM, IgG2, and IgA by in vitro spleen cultures, and (e) had significant decreases in serum levels of IgM, IgG1, IgG2, and IgA. The treated animals failed to make antibodies to ferritin after hyperimmunization, and lacked natural antibodies to sheep erythrocytes. These results indicate that cells ultimately committed to synthesis of IgG1, IgG2, and IgA immunoglobulins are derived from cells which have expressed IgM determinants at an earlier stage of differentiation. They are consistent with a proposed two-stage model for plasma cell differentiation. The first stage is antigen independent, involves sequential activation of Cµ, Cγ, and Cα genes by progeny of a single stem cell, and results in the formation of B lymphocytes bearing membrane-bound recognition antibodies of each class. The second, antigen-dependent, stage results in formation of mature plasmacytes and memory cells.