A role for Toll-like receptors in acquired immunity: up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells.
Toll-like receptors (TLRs) are pattern recognition receptors that trigger innate immunity. In this study we investigated the expression of 10 TLRs in human naive and memory B-cell subsets. We report that in human naive B cells most TLRs are expressed at low to undetectable levels, but the expression of TLR9 and TLR10 is rapidly induced following B-cell-receptor (BCR) triggering. In contrast, memory B cells express several TLRs at constitutively high levels. The differential expression of TLR9 correlates with responsiveness to its agonist, CpG DNA. Thus, human memory B cells proliferate and differentiate to immunoglobulin (Ig)-secreting cells in response to CpG, while naive B do so only if simultaneously triggered through the BCR. The BCR-induced expression of TLRs in human naive B cells prevents polyclonal activation in a primary response, because it restricts stimulation to antigen-specific B cells. In contrast, the constitutive expression of TLRs in memory B cells allows polyclonal activation of the entire memory pool. Thus, in human B cells TLRs are downstream of BCR and play a role both in the primary response and in the memory phase.
Bernasconi
Nadia L
NL
Institute for Research in Biomedicine, Bellinzona, Switzerland. lanzavecchia@irb.unisi.ch
Onai
Nobuyuki
N
Lanzavecchia
Antonio
A
D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000819:agonists / Q000096:biosynthesis* / Q000276:immunology; D015226:Dinucleoside Phosphates / Q000494:pharmacology; D006801:Humans; D007109:Immunity; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000819:agonists / Q000096:biosynthesis* / Q000276:immunology*; D051201:Toll-Like Receptor 10; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D015226:Dinucleoside Phosphates; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D011956:Receptors, Cell Surface; D051201:Toll-Like Receptor 10; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; C495371:TLR9 protein, human; C015772:CpG dinucleotide