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* Institut National de la Santé et de la Recherche Médicale, Unité 851, IFR128 Biosciences Lyon-Gerland, Lyon, France;
Université Claude Bernard Lyon I, Lyon, France; and
Plateau technique de cytométrie en flux, IFR128 Biosciences Lyon-Gerland, Lyon, France
Naive murine B cells are known to proliferate and differentiate in response to LPS or CpG, which bind to TLR4 and TLR9, respectively. However, the naive murine B cell compartment is heterogeneous and comprises four different B cell subsets: B-1a, B-1b, marginal zone (MZ), and follicular (FO) B cells. B-1a, B-1b, and MZ B cells are specialized in the response to thymus-independent Ag, and FO B cells are involved in the response to thymus-dependent Ag. This study was undertaken to compare those four naive B cell subsets for their responses to TLR agonists. Quantitative RT-PCR analysis revealed that expression of TLR transcripts differs quantitatively but not qualitatively from one subset to the other. All TLR agonists, with the exception of flagellin and poly(I:C), stimulate B cell proliferation whatever the subset considered. However, TLR ligation leads to massive differentiation of B-1 and MZ B cells into mature plasma cells (PC) but only marginally promotes PC differentiation of FO B cells. Moreover, TLR stimulation strongly up-regulates expression of Blimp-1 and XBP-1S, two transcription factors known to be instrumental in PC differentiation, in B-1 and MZ B cells but not in FO B cells. Altogether, our findings suggest that B-1 and MZ B cells are poised to PC differentiation in response to the microbial environment and that TLR agonists can be instrumental in stimulating Ab-mediated innate immune protection during microbial infections.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the Institut National de la Santé et de la Recherche Médicale and Sanofi Pasteur.
2 L.G. and M.T. contributed equally to this work and therefore share the first authorship.
3 Address correspondence and reprint requests to Dr. Thierry Defrance, Institut National de la Santé et de la Recherche Médicale Unité 851, IFR 128 BioSciences Lyon-Gerland, 21 Avenue Tony Garnier, Lyon, France. E-mail address: defrance{at}cervi-lyon.inserm.fr
4 Abbreviations used in this paper: FO, follicular; MZ, marginal zone; TI, thymus independent; TD, thymus dependent; PC, plasma cell; HPRT, hypoxanthine guanine phosphoribosyltransferase; ISC, Ig-secreting cell; SN, supernatant.
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