Yan Jun, Wolff Martin J, Unternaehrer Julia, Mellman Ira, Mamula Mark J
Section of Rheumatology, Department of Internal Medicine, Ludwig Institute for Cancer Research, Yale University School of Medicine, 300 Cedar Street, S525, PO Box, 208031 New Haven, CT 06520-8031, USA.
Int Immunol. 2005 Jul;17(7):869-77. doi: 10.1093/intimm/dxh266. Epub 2005 Jun 20.
CD19 is a B cell-surface molecule that participates as an important regulatory signaling complex for antigen bound at the surface by Ig. Triggering of CD19 through its linkage with CD21 amplifies signals transduced through the Src family kinases and modulates B cell differentiation in response to antigen. This study examines the kinetics of antigen uptake and processing of antigen directly targeted to the CD19 protein on purified B cells. We have demonstrated that the antigen internalized within minutes through CD19 forms a cap at the B cell surface and can be found within lysosomes in the cytoplasm in 90 min. B cells acquiring antigen via CD19 express elevated levels of B7-1 and B7-2 co-stimulatory molecules. Moreover, antigen-anti-CD19 complexes administered intravenously bind B cells in vivo and activate antigen-specific T cells more efficiently than non-specific uptake and in a manner similar to antigen taken up through surface IgM on B cells. This work illustrates an important and previously unrecognized mechanism for targeting proteins to B lymphocytes for antigen presentation and activation of CD4 T cells.
CD19是一种B细胞表面分子，作为由Ig结合在表面的抗原的重要调节信号复合物发挥作用。通过与CD21连接触发CD19可放大通过Src家族激酶转导的信号，并调节B细胞对抗原的分化反应。本研究检测了直接靶向纯化B细胞上CD19蛋白的抗原摄取动力学和抗原加工过程。我们已经证明，通过CD19在数分钟内内化的抗原在B细胞表面形成帽状结构，并可在90分钟内在细胞质的溶酶体中发现。通过CD19获取抗原的B细胞表达升高水平的共刺激分子B7-1和B7-2。此外，静脉内给予的抗原-抗CD19复合物在体内结合B细胞，并比非特异性摄取更有效地激活抗原特异性T细胞，其方式类似于通过B细胞表面IgM摄取的抗原。这项工作阐明了一种重要且以前未被认识的机制，即将蛋白质靶向B淋巴细胞以进行抗原呈递和激活CD4 T细胞。
