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

Abstract

Summary 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.

Resting Human Memory B Cells Are Intrinsically Programmed for Enhanced Survival and Responsiveness to Diverse Stimuli Compared to Naive B Cells

“…4a). These results support findings from studies of total peripheral blood or tonsillar B cells (42)(43)(44)(45). TLR9 and TLR10 were expressed at slightly higher levels in memory B cells than in naive B cells (Fig.…”

Potential adjuvantic properties of innate immune stimuli

“…98 Triacyl PAM 3 CSK 4 has been shown to induce IL-6 production in human tonsillar B cells. 99 In addition, PAM 2 CSK 4 and MALP-2 induce isotypic switching and differentiation of naïve human B lymphocytes to IgG-secreting plasma cells, 100 indicating a functional association between BCR stimulation and TLR activation. 100 Triacyl PAM 3 CSK 4 has been shown to dramatically enhance MHC Class I-restricted CTL proliferation to an immunodominant influenza peptide Mx [58][59][60][61][62][63][64][65][66] in a human autologous DC/CD8 + T cell co-culture model.…”

Toll-like receptor agonists in the treatment of chronic lymphocytic leukemia

“…23 However, circulating and tonsillar B cells have been found to make only TLR-1, TLR-2, TLR-7, TLR-9 and TLR-10 proteins, whose expression was not developmentally regulated, suggesting that TLRs are controlled by post-transcriptional mechanisms in human B cells. 24,25 It is notable that, unlike murine B cells, human B cells do not express TLR-4 or respond to LPS.…”