Warnatz Klaus, Salzer Ulrich, Rizzi Marta, Fischer Beate, Gutenberger Sylvia, Böhm Joachim, Kienzler Anne-Kathrin, Pan-Hammarström Qiang, Hammarström Lennart, Rakhmanov Mirzokhid, Schlesier Michael, Grimbacher Bodo, Peter Hans-Hartmut, Eibel Hermann
Department of Rheumatology and Clinical Immunology and Center for Chronic Immunodeficiencies, University Medical Center Freiburg, 79106 Freiburg, Germany.
Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13945-50. doi: 10.1073/pnas.0903543106. Epub 2009 Aug 6.
B-cell survival depends on signals induced by B-cell activating factor (BAFF) binding to its receptor (BAFF-R). In mice, mutations in BAFF or BAFF-R cause B-cell lymphopenia and antibody deficiency. Analyzing BAFF-R expression and BAFF-binding to B cells in common variable immunodeficiency (CVID) patients, we identified two siblings carrying a homozygous deletion in the BAFF-R gene. Removing most of the BAFF-R transmembrane part, the deletion precludes BAFF-R expression. Without BAFF-R, B-cell development is arrested at the stage of transitional B cells and the numbers of all subsequent B-cell stages are severely reduced. Both siblings have lower IgG and IgM serum levels but, unlike most CVID patients, normal IgA concentrations. They also did not mount a T-independent immune response against pneumococcal cell wall polysaccharides but only one BAFF-R-deficient sibling developed recurrent infections. Therefore, deletion of the BAFF-R gene in humans causes a characteristic immunological phenotype but it does not necessarily lead to a clinically manifest immunodeficiency.
B细胞的存活依赖于B细胞活化因子（BAFF）与其受体（BAFF-R）结合所诱导的信号。在小鼠中，BAFF或BAFF-R的突变会导致B细胞淋巴细胞减少和抗体缺陷。通过分析常见变异免疫缺陷（CVID）患者中BAFF-R的表达以及BAFF与B细胞的结合情况，我们鉴定出两名携带BAFF-R基因纯合缺失的同胞。该缺失去除了大部分BAFF-R跨膜部分，导致BAFF-R无法表达。没有BAFF-R，B细胞发育在过渡性B细胞阶段停滞，所有后续B细胞阶段数量严重减少。两名同胞的血清IgG和IgM水平均较低，但与大多数CVID患者不同，他们的IgA浓度正常。他们也未对肺炎球菌细胞壁多糖产生非T细胞依赖性免疫反应，但只有一名BAFF-R缺陷同胞发生反复感染。因此，人类BAFF-R基因的缺失会导致特征性免疫表型，但不一定会导致临床表现出免疫缺陷。
