lymphoproliferative disease gene sap Impaired Ig class switch in mice deficient for the X-linked

Abstract X-linked lymphoproliferative disease is characterized by abnormal immune responses to Epstein-Barr virus attributed to inactivating mutations of the SAP gene. Previous studies showed IgE deficiency and low serum IgG levels in sap -deficient mice before and after viral infections, which are associated with impaired CD4 + T helper function. In the present work, we find that SAP is expressed in B cells and this expression is down-regulated after stimulation with LPS and IL-4. We demonstrate that B cells from sap -deficient mice exhibit reduced IgG and IgA production in vitro . This impairment correlates with decreased circular transcript levels of I , I 2a, I 2b, and I 3 after stimulation, which indicate a defective Ig switch recombination in sap -deficient B cells. While XLP is believed to cause defects in T, NKT, and NK cells, our results indicate that B cells are also affected. From bloodjournal.hematologylibrary.org by guest on June 1, 2013. For personal use only.