A distinct Toll‐like receptor repertoire in human tonsillar B cells, directly activated by Pam3CSK4, R‐837 and CpG‐2006 stimulation

Laboratory of Clinical and Experimental Allergy Research, Department of Otorhinolaryngology, Malmö University Hospital, Lund University, Sweden.
Immunology (Impact Factor: 3.8). 09/2006; 118(4):539-48. DOI: 10.1111/j.1365-2567.2006.02392.x
Source: PubMed


Toll-like receptors (TLRs) recognize specific pathogen-associated molecular patterns (PAMPs), which subsequently trigger innate immunity. Recent data also suggest a role for TLRs in the direct activation of adaptive immune cells. In the present study, the expression and function of TLR1-TLR10 were characterized in purified human tonsillar B cells, focusing on differences among CD19+ CD38- CD27- (naïve B cells), CD19+ IgD- CD27-[germinal centre (GC) B cells] and CD19+ CD38- CD27+ (memory B cells) cells. The study was also designed to compare the TLR expression in B cells obtained from infected and hyperplastic tonsils that served as controls. The results demonstrated a distinct repertoire of TLRs, in which TLR1, TLR2, TLR7, TLR9 and TLR10 predominated. No differences were found among naïve, GC and memory B cells. Tonsillar infection did not substantially alter the TLR expression profile in ex vivo-isolated B-cell subsets. Purified CD19+ B cells stimulated with Pam3CSK4, R-837 and CpG oligodeoxynucleotide (ODN) 2006, via TLR1/TLR2, TLR7 and TLR9, respectively, showed an induction of interleukin-6 secretion and an up-regulated expression of human leucocyte antigen (HLA)-DR. Collectively, the present study demonstrates that B cells exhibit constitutively high levels of specific TLRs, which are not developmentally regulated during the B-cell differentiation process. Ongoing microbial infections, such as chronic tonsillitis, do not appear to affect the TLR profile in B cells. Furthermore, the distinct expression of TLRs allows B cells to respond directly to the cognate PAMPs. This further emphasizes the role of TLRs in directly activating adaptive immune cells.

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    • "They express TLRs and integrate signals from microbial products with B cell receptor signaling and cognate T cell help during the generation of an antibody response (Ruprecht and Lanzavecchia, 2006; Pone et al., 2010; Rawlings et al., 2012). Different B cell subsets express variable levels of TLRs and can respond differently to their ligands, ranging from sustained proliferation, differentiation, and antibody production to the development of immunosuppressive functions (Hornung et al., 2002; Månsson et al., 2006; Crampton et al., 2010; Lampropoulou et al., 2010; Weller et al., 2012). Considering the close interplay of innate and adaptive pathways in B cell responses and the significant role of B cells in infection and protection, it is not surprising that pathogens have been shown to directly interact with and manipulate B lymphocytes . "
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    ABSTRACT: Antibody-mediated immunity to Shigella, the causative agent of bacillary dysentery, requires several episodes of infection to get primed and is short-lasting, suggesting that the B cell response is functionally impaired. We show that upon ex vivo infection of human colonic tissue, invasive S. flexneri interacts with and occasionally invades B lymphocytes. The induction of a type three secretion apparatus (T3SA)-dependent B cell death is observed in the human CL-01 B cell line in vitro, as well as in mouse B lymphocytes in vivo. In addition to cell death occurring in Shigella-invaded CL-01 B lymphocytes, we provide evidence that the T3SA needle tip protein IpaD can induce cell death in noninvaded cells. IpaD binds to and induces B cell apoptosis via TLR2, a signaling receptor thus far considered to result in activation of B lymphocytes. The presence of bacterial co-signals is required to sensitize B cells to apoptosis and to up-regulate tlr2, thus enhancing IpaD binding. Apoptotic B lymphocytes in contact with Shigella-IpaD are detected in rectal biopsies of infected individuals. This study therefore adds direct B lymphocyte targeting to the diversity of mechanisms used by Shigella to dampen the host immune response.
    Full-text · Article · May 2014 · Journal of Experimental Medicine
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    • "Real-time PCR was performed using a Stratagene Mx3000P (Agilent Technologies, Santa Clara, CA, USA). To study PRR expression, FAM™ labeled probes for TLR1-TLR10, NOD1, NOD2, NLRP3, RIG-I, MDA-5, LGP-2 and GAPDH (Applied Biosystems, Foster City, CA, USA) were used as previously described together with Brilliant® QPCR Master Mix (Agilent Technologies) [30], [32], [33]. The thermal cycler was set to perform an initial set-up (95°, 10 min) and 45 cycles of denaturation (95°, 15 sec) followed by annealing/extension (60°, 1 min). "
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    • "Detection of microbes by TLRs evokes an inflammatory response. We, along with several other research groups, have demonstrated functionally active TLRs in nearly all cell types implicated in the pathogenesis of asthma and allergic airway disease, including eosinophils, neutrophils, mast cells, monocytes, dendritic cells, macrophages, B-cells, T-cells, epithelial cells and smooth muscle cells [6], [7], [8], [9], [10], [11]. Accordingly, several TLRs and TLR ligands have been associated with the development of asthma [12]. "
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