SAP is required for generating long-term humoral immunity
SAP is required for generating long-term humoral immunity
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DOI：
10.1038/nature01318
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发表时间：
2003-01-16
期刊：
影响因子：
64.8
通讯作者：
Ahmed, R
中科院分区：
文献类型：
--
作者：
Crotty, S;Kersh, EN;Ahmed, R
长寿浆细胞和记忆B细胞是长期体液免疫的主要细胞成分，因此对大多数疫苗提供的保护至关重要。SAP基因已被确定为X连锁淋巴增生性疾病的遗传位点，X连锁淋巴增生性疾病是一种致命的免疫缺陷(1-4)。SAP中的突变也在一些严重的常见变量免疫缺陷疾病中被发现(5，6)。这种遗传性疾病的潜在细胞基础尚不清楚。我们使用了SAP基因敲除小鼠模型系统来探索SAP在免疫反应中的作用。在这里，我们报告缺乏SAP表达的小鼠在病毒感染后产生强烈的急性抗体反应，但几乎完全没有病毒特异性的长寿浆细胞和记忆B细胞，尽管存在病毒特异性的记忆CD4(+)T细胞。过继转移实验表明SAP缺陷的B细胞是正常的，缺陷的是CD4(+)T细胞。因此，SAP在CD4(+)T细胞功能中起着至关重要的作用：它是晚期B细胞帮助和长期体液免疫发展所必需的，但不是早期B细胞帮助和类别转换所必需的。
Long-lived plasma cells and memory B cells are the primary cellular components of long-term humoral immunity and as such are vitally important for the protection afforded by most vaccines. The SAP gene has been identified as the genetic locus responsible for X-linked lymphoproliferative disease, a fatal immunodeficiency(1-4). Mutations in SAP have also been identified in some cases of severe common variable immunodeficiency disease(5,6). The underlying cellular basis of this genetic disorder remains unclear. We have used a SAP knockout mouse model system to explore the role of SAP in immune responses. Here we report that mice lacking expression of SAP generate strong acute IgG antibody responses after viral infection, but show a near complete absence of virus-specific long-lived plasma cells and memory B cells, despite the presence of virus-specific memory CD4(+) T cells. Adoptive transfer experiments show that SAP-deficient B cells are normal and the defect is in CD4(+) T cells. Thus, SAP has a crucial role in CD4(+) T-cell function: it is essential for late B-cell help and the development of long-term humoral immunity but is not required for early B-cell help and class switching.