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Blood, 15 September 2005, Vol. 106, No. 6, pp. 2069-2075. Prepublished online as a Blood First Edition Paper on June 7, 2005; DOI 10.1182/blood-2004-07-2731. This Article Full Text (PDF) All Versions of this Article: 2004-07-2731v1 106/6/2069    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Al-Alem, U. Articles by Yin, L. Search for Related Content PubMed PubMed Citation Articles by Al-Alem, U. Articles by Yin, L. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 16, 2004 Accepted May 22, 2005 Impaired Ig class switch in mice deficient for the X-linked lymphoproliferative disease gene sap Umaima Al-Alem, Cuiling Li, Nathalie Forey, Francis Relouzat, Marie-Claude Fondaneche, Sean V Tavtigian, Zhao-Qi Wang, Sylvain Latour, and Luo Yin* International Agency for Research on Cancer, Lyon, France; Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University, New York, USA International Agency for Research on Cancer, Lyon, France Unite INSERM 429, Hopital Necker-Enfants Malades, Paris, France * Corresponding author; email: yinluo2005{at}hotmail.com. 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, I2a, I2b, and I3 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 Ig class switching in B cells is also affected. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Q. Chen, J. L. Cannons, J. C. Paton, H. Akiba, P. L. Schwartzberg, and C. M. Snapper A Novel ICOS-Independent, but CD28- and SAP-Dependent, Pathway of T Cell-Dependent, Polysaccharide-Specific Humoral Immunity in Response to Intact Streptococcus pneumoniae versus Pneumococcal Conjugate Vaccine J. Immunol., December 15, 2008; 181(12): 8258 - 8266. [Abstract] [Full Text] [PDF] C. Kamperschroer, D. M. Roberts, Y. Zhang, N.-p. Weng, and S. L. Swain SAP Enables T Cells to Help B Cells by a Mechanism Distinct from Th Cell Programming or CD40 Ligand Regulation J. Immunol., September 15, 2008; 181(6): 3994 - 4003. [Abstract] [Full Text] [PDF] A. Veillette, S. Zhang, X. Shi, Z. Dong, D. Davidson, and M.-C. Zhong SAP expression in T cells, not in B cells, is required for humoral immunity PNAS, January 29, 2008; 105(4): 1273 - 1278. [Abstract] [Full Text] [PDF] G. Roncador, J.-F. G. Verdes-Montenegro, S. Tedoldi, J. C. Paterson, W. Klapper, E. Ballabio, L. Maestre, S. Pileri, M.-L. Hansmann, M. A. Piris, et al. Expression of two markers of germinal center T cells (SAP and PD-1) in angioimmunoblastic T-cell lymphoma Haematologica, August 1, 2007; 92(8): 1059 - 1066. [Abstract] [Full Text] [PDF] I.-J. Kim, C. E. Burkum, T. Cookenham, P. L. Schwartzberg, D. L. Woodland, and M. A. Blackman Perturbation of B Cell Activation in SLAM-Associated Protein-Deficient Mice Is Associated with Changes in Gammaherpesvirus Latency Reservoirs J. Immunol., February 1, 2007; 178(3): 1692 - 1701. [Abstract] [Full Text] [PDF] C. Kamperschroer, J. P. Dibble, D. L. Meents, P. L. Schwartzberg, and S. L. Swain SAP Is Required for Th Cell Function and for Immunity to Influenza J. Immunol., October 15, 2006; 177(8): 5317 - 5327. [Abstract] [Full Text] [PDF] J. L. Cannons, L. J. Yu, D. Jankovic, S. Crotty, R. Horai, M. Kirby, S. Anderson, A. W. Cheever, A. Sher, and P. L. Schwartzberg SAP regulates T cell-mediated help for humoral immunity by a mechanism distinct from cytokine regulation J. Exp. Med., June 12, 2006; 203(6): 1551 - 1565. [Abstract] [Full Text] [PDF] D. B. Graham, M. P. Bell, M. M. McCausland, C. J. Huntoon, J. van Deursen, W. A. Faubion, S. Crotty, and D. J. McKean Ly9 (CD229)-Deficient Mice Exhibit T Cell Defects yet Do Not Share Several Phenotypic Characteristics Associated with SLAM- and SAP-Deficient Mice J. Immunol., January 1, 2006; 176(1): 291 - 300. [Abstract] [Full Text] [PDF]

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