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Blood, 12 November 2009, Vol. 114, No. 20, pp. 4432-4440.
Prepublished online as a Blood First Edition Paper on September 18, 2009; DOI 10.1182/blood-2009-01-200014.


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IMMUNOBIOLOGY

The thymus-independent immunity conferred by a pneumococcal polysaccharide is mediated by long-lived plasma cells

Morgan Taillardet1,2, Ghina Haffar1,2, Paul Mondière1,2, Marie-Jeanne Asensio1,2, Hanane Gheit1,2, Nicolas Burdin3, Thierry Defrance1,2,*, and Laurent Genestier1,2,*

1 Inserm U851, Université de Lyon, L'Institut Fédératif de Recherche (IFR) 128, Lyon; 2 Université Lyon 1, Villeurbanne; and 3 Sanofi Pasteur, Marcy l'Etoile, France

It was recently shown that bacterial thymus-independent (TI) antigens confer long-lasting immunity and generate memory B lymphocytes. However, reactivation of TI memory B cells is repressed in immunocompetent mice, thus raising the issue of the mechanism whereby TI vaccines confer immune protection. Here, we propose an explanation to this apparent paradox by showing that a Streptococcus pneumoniae capsular polysaccharide (PS) generates long-lived bone marrow (BM) plasma cells which frequency can be increased by CpG oligodeoxynucleotides (ODNs). The adjuvant effect of CpG ODNs on the PS3 Ab response is directly targeted to B cells and does not involve B-1a cells. We also demonstrated that BM plasma cells generated in response to the thymus-dependent (TD) form of the PS vaccine have a higher secretion capacity than those produced after immunization with the CpG-adjuvanted PS vaccine. Finally, we show that the PS-specific BM plasma cell compartment is sufficient to confer full protection of vaccinated mice against S pneumoniae infection. Altogether, our results show that TI antigens like their TD counterparts can generate both the lymphoid and the plasma cell component of B-cell memory. They also provide a framework for the improvement and widespread usage of TI vaccines.


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