STAT1在B淋巴球發育及分化上所扮演角色之研究
The Role of STAT1 in B cell Development and differentiation
Date Issued
2005
Date
2005
Author(s)
Liu, Ta-Ming
DOI
en-US
Abstract
B cell development is a tightly regulated process which originates from hematopoiesis stem cells (HSCs) and commits to B-lineage in BM. Mature B cells migrate to spleen and terminally differentiate into antibody-secreting plasma cells after encountering foreign antigens. The complicated B cell developmental progresses are orchestrated by many cytokines and transcriptional cascades. STAT1 is a member of the STAT family which transmits cytokine signals and induces down-stream gene expression. The role of STAT1 in B cell development is still largely unknown. Using ST1KO mice, we have demonstrated that early B lymphopoiesis is impaired in the absence of STAT1, including reduced numbers of pro-B, pre-B, immature-B, and mature-B cells in BM. Interestingly, B220+CD138+ cells of ST1KO mice are also significantly decreased in BM as apposed to WT mice.
In vitro differentiation indicates that reduced Ig production and dysregulation of genes that are critical for plasma cell formation are observed in ST1KO splenocytes upon LPS stimulation. By contrast, comparable Ig production and normal plasma cell differentiation are observed in purified B cell of ST1KO mice after LPS stimulation, implying that the effects seen in splenocytes is through non-B-cell-dependent mechanisms. Interestingly, levels of IL-10 are significantly reduced after LPS stimulation.
To further investigate the role of STAT1 in B cell differentiation, ST1KO mice are immunized with T-dependent (TD) or T-independent (TI) antigens in vivo. Surprisingly, plasma cells of ST1KO mice are dramatically reduced in BM or SP after immunization. Correspondingly, reduced antigen-specific IgM production is observed in response to a TI antigen, and impaired total IgG but not IgM is observed in response to TD antigen. In addition, the failure of class switching into IgG1, IgG2a and IgG2b in ST1KO mice in response to TD antigen, suggesting that this effect is not entirely due to the loss of IFN-γ-responsiveness.
In summary, ST1KO mice reveal defects in early B lymphopoiesis and impaired plasma cell differentiation. This further confirms the unexpected role of STAT1 in humoral immune responses.
Subjects
淋巴球
STAT1
Type
other
File(s)![Thumbnail Image]()
Loading...
Name
ntu-94-R92449007-1.pdf
Size
23.31 KB
Format
Adobe PDF
Checksum
(MD5):63ee02926c7d6602e70e62dc1dcae286