SAP modulates B cell functions in a genetic background-dependent manner

Immunol Lett. 2013 Jun;153(1-2):15-21. doi: 10.1016/j.imlet.2013.06.003. Epub 2013 Jun 24.


Mutations affecting the SLAM-associated protein (SAP) are responsible for the X-linked lympho-proliferative syndrome (XLP), a severe primary immunodeficiency syndrome with disease manifestations that include fatal mononucleosis, B cell lymphoma and dysgammaglobulinemia. It is well accepted that insufficient help by SAP-/- CD4+ T cells, in particular during the germinal center reaction, is a component of dysgammaglobulinemia in XLP patients and SAP-/- animals. It is however not well understood whether in XLP patients and SAP-/- mice B cell functions are affected, even though B cells themselves do not express SAP. Here we report that B cell intrinsic responses to haptenated protein antigens are impaired in SAP-/- mice and in Rag-/- mice into which B cells derived from SAP-/- mice together with wt CD4+ T cells had been transferred. This impaired B cells functions are in part depending on the genetic background of the SAP-/- mouse, which affects B cell homeostasis. Surprisingly, stimulation with an agonistic anti-CD40 causes strong in vivo and in vitro B cell responses in SAP-/- mice. Taken together, the data demonstrate that genetic factors play an important role in the SAP-related B cell functions. The finding that anti-CD40 can in part restore impaired B cell responses in SAP-/- mice, suggests potentially novel therapeutic interventions in subsets of XLP patients.

Keywords: SAP; SLAM-family receptors; XLP.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / transplantation
  • CD40 Antigens / immunology
  • CD40 Antigens / metabolism
  • Homeodomain Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Leukosialin / metabolism
  • Lymphocyte Activation / immunology
  • Lymphoproliferative Disorders / genetics*
  • Lymphoproliferative Disorders / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Signaling Lymphocytic Activation Molecule Associated Protein


  • CD40 Antigens
  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Leukosialin
  • Sh2d1a protein, mouse
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • RAG-1 protein