Analysis of common variable immunodeficiency: approach by memory B cells

常见变异型免疫缺陷（CVID）的分子基础尚不清楚。为了评估CVID中的体液免疫，我们选择了25例早发或迟发疾病患者。根据免疫应答评估、单核细胞或血小板中存在布鲁顿酪氨酸激酶（Btk）以及活化T细胞正常表达CD 40配体，排除X连锁无丙种球蛋白血症（XLA）、X连锁高IgM综合征（XHIM）和非XHIM。所有CVTD患者的循环B细胞数量均在正常范围内。所有25名患者的IgD^-CD 27 ^+记忆B细胞均显著减少，8名患者的IgD^+ CD 27 ^+ B细胞减少。与脐带血B细胞相似，循环B细胞，包括具有IgD^+ CD 27 ^+细胞的CVID患者，在免疫球蛋白V区基因的免疫球蛋白中没有显示出体细胞高突变。CVID患者的B细胞在细胞因子存在下与IG受体和CD 40结合后产生IgM和IgG，但不产生伊加。当在IL-4存在下通过CD 40交联刺激时，除6例患者外，所有患者的B细胞均分泌IgE。对CVID中有缺陷的记忆B细胞的观察表明，与脐带血和高IgM综合征B细胞类似，含有或不含IgD^+ CD 27 ^+的初始CVID B细胞可能是导致不能分化为浆细胞和不能产生高亲和力抗体的原因。

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.