https://scholars.lib.ntu.edu.tw/handle/123456789/560679
標題: | Fcγriib mediates antigen-independent inhibition on human b lymphocytes through btk and p38 mapk | 作者: | SHIANG-JONG TZENG Li W.-Y. Wang H.-Y. |
公開日期: | 2015 | 卷: | 22 | 期: | 1 | 起(迄)頁: | 9 | 來源出版物: | Journal of Biomedical Science | 摘要: | Background: The inhibitory Fc receptor, FcγRIIB, has emerged as a key negative regulator of B cell activation and as such is predicted to play an essential role in controlling antibody-mediated autoimmune diseases in humans. Recent studies have shown that crosslinking the FcγRIIB independently of the B-cell receptor (BCR) results in apoptosis in both mouse and chicken B cells. However, the human B cell subpopulations that are susceptible to BCR-independent, FcγRIIB-mediated regulation are not known. How FcγRIIB mediates this inhibition to affect B cell homeostasis is also not determined. Results: We isolated na?ve B cells, memory B cells and plasma cells (PCs) from peripheral blood of healthy donors and used differentiated PCs in culture to examine the effects on them by FcγRIIB crosslinking. We showed that human PCs, memory and na?ve B cells all expressed FcγRIIB with expression on PCs being the highest in circulation. Moreover, they were sensitive to direct inhibition by FcγRIIB through Btk and p38 MAPK. Similarly, PCs resulting from the antigen-independent differentiation of memory B cells in vitro were inhibited by FcγRIIB cross-linking but memory B cell activation itself, as measured by proliferation, was unaffected. In contrast, both the proliferation and differentiation of na?ve B cells to PCs were blocked by FcγRIIB crosslinking. Conclusion: These results suggest a mechanism to control antibody levels involving the differential expression of FcγRIIB on B cell subpopulations, in which the FcγRIIB functions independently of the BCR to eliminate antibody-secreting effector cells and inhibit na?ve B cell proliferation without compromising the long-lived antigen-specific memory B cells. Importantly, FcγRIIB requires Btk and p38 MAPK to mediate antigen-independent inhibition in human B cells. Taken together, our data underscore the importance of antigen-independent inhibition by FcγRIIB in the prevention from antibody-mediated autoimmune diseases and in the regulation of B cell homeostasis. ? 2015 Tzeng et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/560679 | ISSN: | 10217770 | DOI: | 10.1186/s12929-015-0200-9 | SDG/關鍵字: | Agammaglobulinaemia tyrosine kinase; antigen; Fc receptor; FCGR2B protein, human; mitogen activated protein kinase p38; protein tyrosine kinase; animal; cell differentiation; chicken; human; immunological memory; immunology; mouse; plasma cell; Animals; Antigens; Cell Differentiation; Chickens; Humans; Immunologic Memory; Mice; p38 Mitogen-Activated Protein Kinases; Plasma Cells; Protein-Tyrosine Kinases; Receptors, IgG |
顯示於: | 藥理學科所 |
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