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SAP is required for generating long-term humoral immunity

Abstract

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 immunodeficiency1,2,3,4. Mutations in SAP have also been identified in some cases of severe common variable immunodeficiency disease5,6. 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.

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Figure 1: Defective long-term humoral immune responses in SAP- mice.
Figure 2: CD4+ T-cell functional analysis.
Figure 3: SAP expression is not required in B cells for long-term humoral memory.
Figure 4: SAP expression is required in CD4+ TH cells to generate long-term humoral immunity.
Figure 5: SAP expression requirements for generating long-term humoral immunity.

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Acknowledgements

We thank L. Mijares for technical assistance, and J. Gibson Lanier and D. Barber for expertise. This work was supported by intramural and extramural NIH funding. S.C. is a Cancer Research Institute postdoctoral fellow.

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Correspondence to Rafi Ahmed.

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Crotty, S., Kersh, E., Cannons, J. et al. SAP is required for generating long-term humoral immunity. Nature 421, 282–287 (2003). https://doi.org/10.1038/nature01318

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