Analysis of common variable immunodeficiency: approach by memory B cells

常见变异型免疫缺陷的分析：记忆 B 细胞的方法

基本信息

批准号：
12670737
负责人：
AGEMATSU Kazunaga
金额：
$ 2.11万
依托单位：
Shinshu Univ.
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670737/
关键词：
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

项目摘要

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.

公共可变免疫缺陷（CVID）的分子基础尚不清楚。为了评估CVID的体液免疫力，我们选择了25例疾病早期或晚期的患者。 X连锁的AGAMMAGLOBULINEMIA（XLA），X连接的高IGM综合征（XHIM）和非XHIM被排除在于免疫反应的评估，在单核细胞或血小板和正常表达中通过激活的T细胞在单核细胞或血小板中的存在，并存在Bruton的酪氨酸激酶（BTK）。在所有CVTD患者中，循环B细胞的数量均在正常范围内。 IgD^-CD27^+记忆B细胞在所有25例患者中明显降低，IgD^+ CD27^+ B细胞在8例患者中均降低。循环的B细胞，包括IgD^+ CD27^+细胞的CVID患者，在免疫原子素（V） - 区域基因中没有显示出与脐带血B细胞相似的免疫原子体中的超数。来自CVID患者的B细胞产生IgM和IgG，但在Ig受体和CD40的参与下，IgA并非IgA。当IL-4存在的CD40刺激CD40刺激时，来自除6例患者的B细胞分泌IgE。 CVID中有缺陷的记忆B细胞的观察表明，具有或不具有IgD^+ CD27^+的天真CVID B细胞类似于脐带血和超级IGM综合征B细胞，可能导致分化为血浆细胞的失败和高亲和抗体的产生。