The toll-like receptor repertoire of human B lymphocytes: inducible and selective expression of TLR9 and TLR10 in normal and transformed cells.
The present study was designed to investigate the expression of members of the toll-like receptor (TLR) family in human B cells. High-density, resting, and low-density activated tonsillar B cells expressed TLR9 and TLR10 mRNA transcripts at the highest levels. Expression was higher in activated B cells than in resting cells. Analysis of a range of resting and activated human leukocyte populations revealed that mRNA expression of TLR10 was restricted to B cells. Stimulation of resting B cells with anti-mu and anti-CD40 antibodies or with Staphylococcus aureus Cowan I bacteria (SAC) increased expression of TLR9 and TLR10. TLR1 and TLR4 expression were not significantly induced by B-cell activation. Interestingly, a CpG oligonucleotide, a TLR9 agonist, also stimulated TLR9 expression in B cells. Exposure to anti-mu antibodies augmented TLR9 expression, concomitantly and dramatically increasing the responsiveness of B cells to CpG oligonucleotides in terms of proliferation and chemokine (CC chemokine ligand 3 [CCL3] and CCL22) production. Epstein-Barr virus (EBV)-transformed cell lines and other cell lines representative of mature B-cell neoplasias (Burkitt lymphoma, follicular lymphoma, multiple myeloma) expressed TLR9 and/or TLR10, whereas pre-B cell lines were negative. These results show that normal and neoplastic human B lymphocytes express a distinct TLR repertoire including TLR9 and TLR10 and that expression is increased upon engagement of the antigen receptor complex or TLR9 itself. Regulated expression of selected TLRs in B cells is likely to play an important role in linking innate and adaptive immune responses in normal and pathologic conditions.
Bourke
Emer
E
Department of Immunology and Cell Biology, Mario Negri Institute, Milan, Italy.
Bosisio
Daniela
D
Golay
Josee
J
Polentarutti
Nadia
N
Mantovani
Alberto
A
D001402:B-Lymphocytes / Q000378:metabolism*; D002461:Cell Line, Transformed; D018899:CpG Islands; D004268:DNA-Binding Proteins / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D009841:Oligonucleotides / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics; D051194:Toll-Like Receptor 1; D051201:Toll-Like Receptor 10; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors
D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D009841:Oligonucleotides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C475955:TLR10 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051194:Toll-Like Receptor 1; D051201:Toll-Like Receptor 10; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors