Hasegawa M, Fujimoto M, Poe J C, Steeber D A, Tedder T F
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
J Immunol. 2001 Sep 15;167(6):3190-200. doi: 10.4049/jimmunol.167.6.3190.
B lymphocytes are critically regulated by signals transduced through the CD19-CD21 cell surface receptor complex, where complement C3d binding to CD21 supplies an already characterized ligand. To determine the extent that CD19 function is controlled by complement activation, CD19-deficient mice (that are hyporesponsive to transmembrane signals) and mice overexpressing CD19 (that are hyperresponsive) were crossed with CD21- and C3-deficient mice. Cell surface CD19 and CD21 expression were significantly affected by the loss of CD21 and C3 expression, respectively. Mature B cells from CD21-deficient littermates had approximately 36% higher cell surface CD19 expression, whereas CD21/35 expression was increased by approximately 45% on B cells from C3-deficient mice. Negative regulation of CD19 and CD21 expression by CD21 and C3, respectively, may be functionally significant because small increases in cell surface CD19 overexpression can predispose to autoimmunity. Otherwise, B cell development and function in CD19-deficient and -overexpressing mice were not significantly affected by a simultaneous loss of CD21 expression. Although CD21-deficient mice were found to express a hypomorphic cell surface CD21 protein at low levels that associated with mouse CD19, C3 deficiency did not significantly affect B cell development and function in CD19-deficient or -overexpressing mice. These results, and the severe phenotype exhibited by CD19-deficient mice compared with CD21- or C3-deficient mice, collectively demonstrate that CD19 can regulate B cell signaling thresholds independent of CD21 engagement and complement activation.
B淋巴细胞受到通过CD19 - CD21细胞表面受体复合物转导的信号的严格调控，其中补体C3d与CD21的结合提供了一个已被表征的配体。为了确定CD19功能受补体激活控制的程度，将CD19缺陷小鼠（对跨膜信号反应低下）和过表达CD19的小鼠（反应过度）与CD21和C3缺陷小鼠进行杂交。细胞表面CD19和CD21的表达分别受到CD21和C3表达缺失的显著影响。来自CD21缺陷同窝小鼠的成熟B细胞，其细胞表面CD19表达大约高36%，而来自C3缺陷小鼠的B细胞上CD21/35表达增加了约45%。CD21和C3分别对CD19和CD21表达的负调控在功能上可能具有重要意义，因为细胞表面CD19过表达的微小增加可能易引发自身免疫。否则，CD19缺陷和过表达小鼠中的B细胞发育和功能不会因CD21表达的同时缺失而受到显著影响。虽然发现CD21缺陷小鼠表达低水平的与小鼠CD19相关的亚型细胞表面CD21蛋白，但C3缺陷对CD19缺陷或过表达小鼠中的B细胞发育和功能没有显著影响。这些结果，以及与CD21或C3缺陷小鼠相比CD19缺陷小鼠表现出的严重表型，共同表明CD19可以独立于CD21结合和补体激活来调节B细胞信号转导阈值。
