SAP expression in invariant NKT cells is required for cognate help to support B-cell responses

Cynthia Detre, Marton Keszei, Natividad Garrido-Mesa, Katalin Kis-Toth, Wilson Castro, Amma F Agyemang, Natacha Veerapen, Gurdyal S Besra, Michael C Carroll, George C Tsokos, Ninghai Wang, Elizabeth A Leadbetter, Cox Terhorst

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


One of the manifestations of X-linked lymphoproliferative disease (XLP) is progressive agammaglobulinemia, caused by the absence of a functional signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) in T, invariant natural killer T (NKT) cells and NK cells. Here we report that α-galactosylceramide (αGalCer) activated NKT cells positively regulate antibody responses to haptenated protein antigens at multiple checkpoints, including germinal center formation and affinity maturation. Whereas NKT cell-dependent B cell responses were absent in SAP(-/-).B6 mice that completely lack NKT cells, the small number of SAP-deficient NKT cells in SAP(-/-).BALB/c mice adjuvated antibody production, but not the germinal center reaction. To test the hypothesis that SAP-deficient NKT cells can facilitate humoral immunity, SAP was deleted after development in SAP(fl/fl).tgCreERT2.B6 mice. We find that NKT cell intrinsic expression of SAP is dispensable for noncognate helper functions, but is critical for providing cognate help to antigen-specific B cells. These results demonstrate that SLAM-family receptor-regulated cell-cell interactions are not limited to T-B cell conjugates. We conclude that in the absence of SAP, several routes of NKT cell-mediated antibody production are still accessible. The latter suggests that residual NKT cells in XLP patients might contribute to variations in dysgammaglobulinemia.
Original languageEnglish
Pages (from-to)122-9
Number of pages8
Issue number1
Publication statusPublished - 2012


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