SAP is required for generating long-term humoral immunity

被引:347
作者
Crotty, S
Kersh, EN
Cannons, J
Schwartzberg, PL
Ahmed, R [1 ]
机构
[1] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA
[2] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA
[3] NHGRI, NIH, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nature01318
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:282 / 287
页数:7
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