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患者的体液免疫功能，我们选择了25名起病早或晚的患者。根据免疫反应、单核细胞或血小板中存在Bruton‘s酪氨酸激酶(BTK)、活化T细胞CD40配体表达正常，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。25例患者IGD~+CD27~+记忆B细胞均明显减少，8例患者IGD~+CD27~+B细胞减少。循环B细胞，包括具有IGD+CD27+细胞的CVID患者，与脐带血B细胞相似，未表现出免疫球蛋白Vanaoie(V)区基因的体细胞高突变。CVID患者的B细胞在细胞因子存在的情况下，Ig受体与CD40结合后产生IgM和Ig G，但不产生Ig A。除6例患者外，其余患者的B细胞在有IL-4存在的CD40交联剂刺激下均可分泌IgE。对CVID患者记忆缺陷B细胞的观察表明，无论有无IGD+CD27+的幼稚CVID B细胞，类似于脐带血和高IgM综合征B细胞，可能是导致其不能分化为浆细胞并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.