A Role for Lysosomal-Associated Protein Transmembrane 5 in the Negative Regulation of Surface B Cell Receptor Levels and B Cell Activation
A Role for Lysosomal-Associated Protein Transmembrane 5 in the Negative Regulation of Surface B Cell Receptor Levels and B Cell Activation
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DOI：
10.4049/jimmunol.1000371
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发表时间：
2010-07-01
影响因子：
4.4
通讯作者：
Wang, Ji-Yang
中科院分区：
文献类型：
--
作者：
Ouchida, Rika;Kurosaki, Tomohiro;Wang, Ji-Yang
调节BCR细胞表面水平的机制在很大程度上仍不清楚。我们发现，在体内外，缺乏溶酶体相关蛋白跨膜5(LAPTM5)的B细胞在Ag刺激后比野生型(WT)B细胞表达更高水平的细胞表面bcr。此外，LAPTM5缺乏的小鼠在T依赖的Ag免疫后，比WT小鼠含有更多的Ag特异性B细胞，并产生更多的抗体。将LAPTM5缺陷的B细胞和WT细胞过继转移到RAG1缺陷的小鼠体内，结果显示表面bcr水平的升高以及B细胞活化和抗体产生的增加是由于B细胞的固有缺陷。随着年龄的增长，LAPTM5缺陷小鼠的血清IgM和自身抗体滴度增加，肾脏中免疫复合体沉积。免疫荧光和生化分析表明，LAPTM5与BCR复合体在物理上相互作用，并促进其在小鼠B细胞溶酶体中的降解。这些结果表明LAPTM5在细胞表面bcr水平和B细胞活化的负性调节中起作用。免疫学杂志，2010,185：294-301。
Mechanisms by which cell surface levels of the BCR are regulated remain largely unknown. We found that B cells lacking the lysosomal-associated protein transmembrane 5 (LAPTM5) expressed higher levels of cell surface BCR than did wild-type (WT) B cells after Ag stimulation in vitro and in vivo. In addition, LAPTM5-deficient mice contained an increased frequency of Ag-specific B cells and produced greater amounts of Abs than did WT mice after immunization with a T-dependent Ag. Adoptive transfer of LAPTM5-deficient B cells with WT T cells into RAG1-deficient mice revealed that the increased surface BCR levels and the enhanced B cell activation and Ab production were due to a B cell intrinsic defect. As they aged, the LAPTM5-deficient mice had increased titers of serum IgM and autoantibodies and immune complex deposition in the kidney. Immunofluorescent and biochemical analysis revealed that LAPTM5 physically interacted with the BCR complex and promoted its degradation in the lysosomal compartment in mouse B cells. These results demonstrate a role for LAPTM5 in the negative regulation of cell surface BCR levels and B cell activation. The Journal of Immunology, 2010, 185: 294-301.