期刊
MOLECULAR IMMUNOLOGY
卷 88, 期 -, 页码 135-137出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2017.05.023
关键词
BCR; Rituximab; CD20; BAFF-R; Autoimmune diseases; Lymphoma
资金
- research committee of the Kuopio University Hospital Catchment Area
- North-Savo cancer organization
- Doctoral programme of Molecular Medicine of University of Eastern Finland
Antibodies produced by B-cells provide protection from infectious agents. However, impaired cell death signaling pathways in B-cells can lead to cancer, immunodeficiency or autoimmune diseases. B-cell signaling molecules such as CD20, CD19, Btk, and BAFF-R are targeted by therapeutic drugs and used to treat B-cell derived lymphomas or autoimmune diseases. Nevertheless, B-cells could develop resistance to these therapeutic drugs or the therapeutic drugs may have off-target effects. For instance, repeated rituximab (anti-CD20 antibody) treatment may lead to the loss of its target cell surface molecule, CD20. In addition, in B-cell malignancies, loss of CD19 expression has been observed. Another target molecule, Btk is expressed not only in B-cells but also in mast cells, macrophages, and dendritic cells. Thus, targeting Btk could negatively regulate the functions of innate immunity. The expression of BAFF-R is thought to be restricted to B-cells but it is also expressed on T cells. Targeting BAFF-R, therefore, may lead to depletion of T-cells in addition to B-cells. B cell receptor (BCR) expression and signaling, however, are critically important for development, differentiation and survival of B cells. Moreover, BCR is exclusively expressed on B-cells, which makes it an excellent target to avoid off-target effects.
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