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* Institut National de la Santé et de la Recherche Médicale, Unité 547;
Institut Pasteur de Lille, Institut Fédératif de Recherche 142; and
Université de Lille 2, Lille, France
Splenic marginal zone B (MZB) lymphocytes represent, along with dendritic cells (DC) a first line of defense against blood-borne pathogens. MZB cells express high levels of MHC class II and CD1d molecules but so far their ability to activate and orientate conventional and innate-like T lymphocytes, such as invariant NKT (iNKT) cells, is still elusive. In the present study, we show that murine MZB cells proliferate, mature phenotypically, and secrete cytokines in response to TLR (except TLR3) agonists. When pulsed with OVA peptide (but not whole OVA), MZB cells promote the release of IFN-
and IL-4 by Ag-specific CD4+ T lymphocytes and their stimulation with the TLR9 agonist CpG oligodeoxynucleotide (ODN), a potent MZB cell activator, biases them toward more Th1 inducers. Unlike DC, CpG ODN-stimulated MZB cells fail to stimulate iNKT cells. Although able to activate iNKT hybridomas, MZB cells sensitized with free 
-galactosylceramide (-GalCer), a CD1d-restricted glycolipid Ag, do not directly activate ex vivo sorted iNKT cells unless DC are added to the culture system. Interestingly, MZB cells amplify the DC-mediated activation of iNKT cells and depletion of MZB cells from total splenocytes strongly reduces iNKT cell activation (cytokine production) in response to -GalCer. Thus, DC and MZB cells provide help to each other to optimize iNKT cell stimulation. Finally, in vivo transfer of -GalCer-loaded MZB cells potently activates iNKT and NK cells. This study confirms and extends the concept that MZB cells are important players in immune responses, a property that might be exploited.
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1 This work was supported by the Institut National de la Santé et de la Recherche Médicale, the Pasteur Institute of Lille, the University of Lille 2 and the Contrat de Plan Etat Région 2006–2008/Fonds Européen de Développement Régional. E.B. and C.P. are recipients of a doctoral fellowship from the Ministère de l’Enseignement Supérieur et de la Recherche and the Conseil Régional Nord-Pas-de-Calais/Institut National de la Santé et de la Recherche Médicale, respectively. C.F. is supported by the Institut National de la Santé et de la Recherche Médicale and F.T. by the Centre National de la Recherche Scientifique.
2 Address correspondence and reprint requests to Dr. Christelle Faveeuw, Unité Inserm U547, Institut Pasteur de Lille, 1 rue du Professeur Calmette, 59019 Lille Cedex, France. E-mail address: christelle.faveeuw{at}pasteur-lille.fr
3 Abbreviations used in this paper: MZB, marginal zone B; DC, dendritic cell; CpG ODN, CpG oligodeoxynucleotide; -GalCer, -galactosylceramide; iNKT, invariant NKT; MNC, mononuclear cell; WT, wild type.
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