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Blood, 8 January 2009, Vol. 113, No. 2, pp. 370-376. Prepublished online as a Blood First Edition Paper on October 2, 2008; DOI 10.1182/blood-2008-06-166249. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-06-166249v1 113/2/370    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 Tonti, E. Articles by Dellabona, P. Search for Related Content PubMed PubMed Citation Articles by Tonti, E. Articles by Dellabona, P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 30, 2008 Accepted September 12, 2008 NKT cell help to B lymphocytes can occur independently of cognate interaction Elena Tonti, Grazia Galli, Carmine Malzone, Sergio Abrignani, Giulia Casorati, and Paolo Dellabona* Experimental Immunology Unit, Cancer Immunotherapy and Gene Therapy Program, DBIT, H. San Raffaele Scientific Institute, Milan, Italy Novartis Vaccines, Siena, Italy Instituto Nationale di Genetica Molecolare, Milan, Italy * Corresponding author; email: dellabona.paolo{at}hsr.it. CD4+ T (Th) cell help to B lymphocytes requires cognate interaction and CD40 engagement. Invariant (i)NKT cells are innate-like T lymphocytes that recognize GalactosylCeramide (GalCer) presented by CD1d, and can help B cell responses. We asked whether GalCer-activated iNKT cells help B lymphocytes through cognate interaction, or indirectly, via enhancement of Th-B cells interaction. After immunization with protein Ags and GalCer, antibody titers were assessed in wild type or splenectomized mice, and in bone marrow radiation chimeras (BMCs) lacking CD1d or CD40 expression on B lymphocytes, or expressing CD1d or MHC II disjointly on antigen-presenting cells (APCs). We find that GalCer-dependent enhancement of B cell response: (i) can occur when B cells do not express CD1d but express CD40; (ii) requires that iNKT and Th cells interact with the same APCs that co-express both CD1d and MHC class II; (iii) takes place without spleen. These findings demonstrate GalCer-induced help for antibody responses can occur without cognate iNKT/B cell interaction, and suggest this help entails activation of APCs by iNKT cells, which in turn activate Th cells and their helper functions for B cells. Thus the GalCer-induced help recapitulates the function of classical adjuvants that stimulate the innate immune system to support adaptive immune responses. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. L. Allan, K. Hoefl, D.-J. Zheng, B. K. Chung, F. K. Kozak, R. Tan, and P. van den Elzen Apolipoprotein-mediated lipid antigen presentation in B cells provides a pathway for innate help by NKT cells Blood, September 17, 2009; 114(12): 2411 - 2416. [Abstract] [Full Text] [PDF] M. Fedeli, A. Napolitano, M. P. M. Wong, A. Marcais, C. de Lalla, F. Colucci, M. Merkenschlager, P. Dellabona, and G. Casorati Dicer-Dependent MicroRNA Pathway Controls Invariant NKT Cell Development J. Immunol., August 15, 2009; 183(4): 2506 - 2512. [Abstract] [Full Text] [PDF] E. Bialecki, C. Paget, J. Fontaine, M. Capron, F. Trottein, and C. Faveeuw Role of Marginal Zone B Lymphocytes in Invariant NKT Cell Activation J. Immunol., May 15, 2009; 182(10): 6105 - 6113. [Abstract] [Full Text] [PDF]

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