TLR Agonists Selectively Promote Terminal Plasma Cell Differentiation of B Cell Subsets Specialized in Thymus-Independent Responses

Institut National de la Santé et de la Recherche Médicale Unité 851, IFR128 Biosciences Lyon-Gerland, 21 Avenue Tony Garnier, Lyon, France.
The Journal of Immunology (Impact Factor: 4.92). 07/2007; 178(12):7779-86. DOI: 10.4049/jimmunol.178.12.7779
Source: PubMed


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-1(S), 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.

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    • "Our result also confirmed this abnormality (Figure S4). MZ B cells are programmed for efficient differentiation into mature plasma cells with the ability to secrete massive quantities of IgM in response to TLR agonists such as LPS [42]. In addition, MZ B cells have an enhanced secretory apparatus [43] and lower activation thresholds [44]. "
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    • "Experimental evidence abounds on the ability of Myd88 to influence immune and inflammatory signaling through multiple pathways, and protective immunity against many pathogens [26,28,34,35,36,37,38,39]. In view of reports suggesting the important roles played by Myd88 signaling in the generation of humoral immune responses, we explored the potential utility of Myd88 as a genetic adjuvant in plasmid vaccination against rabies. "
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    • "Upon stimulation with IL-6, 12-O-tetradecanoylphorbol-13-acetate (TPA) or lipopolysaccharide (LPS), B cells are activated, rapidly proliferate and initiate differentiation processes leading to increased antibody secretion, e.g., immunoglobulin M (IgM) [19,21,22,25,26]. To determine which stimulator was most efficient for the present study, we treated SKW 6.4 cells with rhIL-6 (50-1600 U/ml), TPA (1-1000 nM) or LPS (1-5 μM) for 4 days. "
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