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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.

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IMMUNOBIOLOGY

NKT-cell help to B lymphocytes can occur independently of cognate interaction

Elena Tonti1, Grazia Galli2, Carmine Malzone2, Sergio Abrignani3, Giulia Casorati1, and Paolo Dellabona1

1 Experimental Immunology Unit, Cancer Immunotherapy and Gene Therapy Program, DIBIT, H. San Raffaele Scientific Institute, Milano; 2 Novartis Vaccines, Siena; and 3 Istituto Nazionale di Genetica Molecolare, Milan, Italy

CD4+ T (Th)–cell help to B lymphocytes requires cognate interaction and CD40 engagement. Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that recognize {alpha}galactosylceramide ({alpha}GalCer) presented by CD1d, and can help B-cell responses. We asked whether {alpha}GalCer-activated iNKT cells help B lymphocytes through cognate interaction, or indirectly, via enhancement of Th-B–cell interaction. After immunization with protein Ags and {alpha}GalCer, antibody titers were assessed in wild-type or splenectomized mice, and in bone marrow radiation chimeras lacking CD1d or CD40 expression on B lymphocytes, or expressing CD1d or MHC II disjointly on antigen-presenting cells (APCs). We find that {alpha}GalCer-dependent enhancement of B-cell response (1) can occur when B cells do not express CD1d but express CD40; (2) requires that iNKT and Th cells interact with the same APCs that coexpress both CD1d and MHC-II; and (3) takes place without spleen. These findings demonstrate {alpha}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 {alpha}GalCer-induced help recapitulates the function of classical adjuvants that stimulate the innate immune system to support adaptive immune responses.


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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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