hematopoietic system
• with pIpC treatement, B cell development in bone marrow is severely impaired; pro-B, pre-B, and immunoglobulin IgM+ B cells are drastically reduced in number, whereas prepro-B cell numbers are increased with pIpC treatment
• prepro-B cells express elevated levels of T cell-specific target genes and appear to aberrantly committed to the T cell lineage despite B220 expression; in culture, pIpC-treated cells lose B220 expression and differentiate into CD4/8 double positive T cells
• inhibition of Notch signaling by treatment with a gamma secretase inhibitor (GSI) rescues B or T cell commitment abnormalities
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• accumulation of extrathymic double-positive T cells is seen in bone marrow of pIpC treated mice, with these cells accounting for ~30% of bone marrow mononuclear cells 1 month after pIpC treatment; these DP T cells are not found in spleen or Peyer's patches
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• after injection of polyinosinic:polycytidylic acid (pIpC) at 2 week intervals starting at 3 weeks of age to induce cre expression, significant decline in white blood cells is observed relative to untreated controls
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• reduction in B220+ B cells with polyinosinic:polycytidylic acid-induced cre induction
• however, T cell numbers remain similar to controls
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• with pIpC treatment, slightly increased numbers are observed with pIpC treatment; numbers of common lyphoid progenitor (CLP) cells are also slightly elevated
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immune system
N |
• slight decrease in double-negative 3 (DN3) and double-negative 4 (DN4) thymocyte populations is seen, but proportions of CD4 single-positive, CD8 single-positive, and CD4/8 double-positive T cells are comparable to control mice after pIpC treatment
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• with pIpC treatement, B cell development in bone marrow is severely impaired; pro-B, pre-B, and immunoglobulin IgM+ B cells are drastically reduced in number, whereas prepro-B cell numbers are increased with pIpC treatment
• prepro-B cells express elevated levels of T cell-specific target genes and appear to aberrantly committed to the T cell lineage despite B220 expression; in culture, pIpC-treated cells lose B220 expression and differentiate into CD4/8 double positive T cells
• inhibition of Notch signaling by treatment with a gamma secretase inhibitor (GSI) rescues B or T cell commitment abnormalities
|
• accumulation of extrathymic double-positive T cells is seen in bone marrow of pIpC treated mice, with these cells accounting for ~30% of bone marrow mononuclear cells 1 month after pIpC treatment; these DP T cells are not found in spleen or Peyer's patches
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• after injection of polyinosinic:polycytidylic acid (pIpC) at 2 week intervals starting at 3 weeks of age to induce cre expression, significant decline in white blood cells is observed relative to untreated controls
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• reduction in B220+ B cells with polyinosinic:polycytidylic acid-induced cre induction
• however, T cell numbers remain similar to controls
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• when cells from these mice are transferred to lethally irradiated recipients, upon pIpC treatment, donor-derived double positive T cells accumulate in bone marrow and peripheral blood
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