How self-tolerance and the immunosuppressive drug FK506 prevent B-cell mitogenesis
Article Abstract:
It has been possible to develop the first molecular explanation for how self-tolerance prevents lymphocyte mitogenesis. This research has used gene-expression arrays to explain the loss of mitogenic response in peripheral B-cell anergy, an element of immunological tolerance. The loss of mitotic response to antigen is attributable to failure to upregulate LSIRF, a B-cell myeloma protooncogene that is a vital transcription factor for B-cell mitogenic responses, and failure to upregulate A1, an anti-apoptotic protein that seems to be required to block apoptotic responses to antigen in B cells. Inhibition of A1 induction by the immunosuppressant FK506 could by itself be sufficient to explain the anti-mitogenic effects of FK506.
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 2000
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Regulation of B-lymphocyte negative and positive selection by tyrosine phosphatase CD45
Article Abstract:
A cross between tyrosine phosphatase CD45-deficient mice and mice carrying immunoglobulin transgenes specific for hen egg lysozyme (HEL) shows that CD45 positively regulates antigen-receptor signaling. CD45-deficient HEL-specific B cells show diminished signaling in response to HEL. Circulating HEL autoantigen controls negative selection of mature CD45(super +/+) HEL-binding B cells. The autoantigen positively selects CD45(super -/-) HEL-binding B cells. Inherited susceptibility to autoimmune disease is possible due to changes in antigen receptor signaling.
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 1996
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Differential activation of transcription factors induced by Ca2+ response amplitude and duration
Article Abstract:
A diverse range of cell functions, such as adhesion, gene expression and proliferation, are controlled by a rise in intracellular calcium ion concentrations (Ca2+). The differential activation of pro-inflammatory transcriptional regulators is controlled by the amplitude and duration of calcium signals in B lymphocytes. Information in the amplitude and duration of Ca2+ signals can be decoded by downstream effectors.
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 1997
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