| Project/Area Number |
12670737
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Shinshu Univ. |
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Principal Investigator |
AGEMATSU Kazunaga Shinshu Univ. Sch. of Med., Dept. Pediatr., Asociate prof., 大学院・医学研究科, 助教授 (60262721)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Common variable immunodeficiency / Memory B cells / CD27 / immunological memory / Naive B cells / 低γグロブリン血症 / CD27 / CD70相互作用 / 免疫グロブリン産生 |
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| Research Abstract |
The molecular basis of common variable immunodeficiency ( CVID ) remains unclear. To assess humoral immunity in CVID, we selected 25 patients with early or late onset of disease. X-linked agammaglobulinemia ( XLA ), X-linked hyper-IgM syndrome ( XHIM ) and non-XHIM were excluded based on assessment of the immune response, presence of Bruton's tyrosine kinase ( Btk ) in monocytes or platelets and normal expression of CD40 ligand by activated T cells. The number of circulating B cells was within normal range in all CVTD patients. IgD^- CD27^+ memory B-cells were markedly reduced in all 25 patients and IgD^+ CD27^+ B-cells were diminished in 8 patients. Circulating B cells, including the CVID patients with IgD^+ CD27^+ cells, did not demonstratesomatic hypermutation in immunoglo in immunogioouiin vanaoie ( V )- region genes, similar to cord blood B cells. B cells from CVID patients produced IgM and IgG, but not IgA upon the engagement of Ig receptor and CD40 in the presence of cytokines. B cells from all but 6 patients secreted IgE when stimulated by CD40 crosslinking in the presence of IL-4. The observation of defective memory B cells in CVID demonstrates that naive CVID B cells with or without IgD^+ CD27^+, in analogy to cord blood and hyper IgM syndrome B cells, may be responsible for the failure of the differentiation into plasma cells and the production of high affinity antibodies.
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