Regulation of B lymphocyte development and activation by the CD19/CD21/CD81/Leu 13 complex requires the cytoplasmic domain of CD19.
Regulation of B lymphocyte development and activation by the CD19/CD21/CD81/Leu 13 complex requires the cytoplasmic domain of CD19.
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DOI：
10.4049/jimmunol.159.7.3278
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发表时间：
1997-10
影响因子：
4.4
通讯作者：
Shinichi Sato;Ann S. Miller;M. Howard;Thomas F. Tedder
中科院分区：
文献类型：
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作者：
Shinichi Sato;Ann S. Miller;M. Howard;Thomas F. Tedder
B 淋巴细胞的发育和功能部分受到 CD19 细胞表面受体复合物的调节，该复合物由至少四种蛋白质组成； CD19、CD21（CR2、补体受体 2）、CD81 和 Leu 13。由于该复合物具有 8 个跨膜结构域和 6 个细胞质区域，因此确定其功能和信号转导活性的分子基础并不简单。在这项研究中，通过生成表达仅编码 CD19 胞外和跨膜结构域的转基因的 CD19 缺陷型小鼠，评估了 CD19 胞质结构域对 CD19/CD21/CD81/Leu 13 复合物体内功能的贡献。表达这种转基因的小鼠与 CD19 缺陷小鼠相似（如果不是相同的话），这些小鼠具有异常 B 细胞发育、缺乏 B-1 细胞、B 细胞表面 IgM 水平升高、适度的丝裂原反应、最低的血清 Ig 水平和低体液免疫反应。这项研究的结果表明，通过 CD19 胞质结构域产生的特异性信号对于 B 淋巴细胞的发育和功能至关重要，并且 CD19 是 CD19 复合物的主要信号传导成分。此外，CD19 胞质结构域的表达是通过 B 细胞 Ag 受体复合物实现最佳信号传导所必需的。
B lymphocyte development and function are regulated in part by the CD19 cell surface receptor complex, which is composed of at least four proteins; CD19, CD21 (CR2, complement receptor 2), CD81, and Leu 13. Because this complex has eight membrane-spanning domains and six cytoplasmic regions, determining the molecular basis for its function and signal transduction activities has not been straightforward. In this study, the contribution of the CD19 cytoplasmic domain to the in vivo function of the CD19/CD21/CD81/Leu 13 complex was assessed by generating CD19-deficient mice that expressed a transgene that encoded only the extracellular and transmembrane domains of CD19. Mice expressing this transgene were similar, if not identical, to CD19-deficient mice with abnormal B cell development, a lack of B-1 cells, increased surface IgM levels on B cells, modest mitogen responses, minimal serum Ig levels, and low humoral immune responses. The results of this study indicate that specific signals generated through the cytoplasmic domain of CD19 are essential for B lymphocyte development and function, and that CD19 is the dominant signaling component of the CD19 complex. Moreover, expression of the CD19 cytoplasmic domain is required for optimal signaling through the B cell Ag receptor complex.