Characterization of the B-cell inhibitory protein factor in Ixodes ricinus tick saliva: a potential role in enhanced Borrelia burgdoferi transmission.
We recently described the inhibition of host B lymphocytes by Ixodes ricinus tick saliva. In this study, we characterized the factor responsible for this activity and examined the modulation of lipopolysaccharide (LPS)- and Borrelia burgdorferi outer surface protein (Osp)-induced proliferation of naive murine B lymphocytes by an enriched fraction of this factor. The B-lymphocyte inhibitory activity was destroyed by trypsin treatment, indicating that a proteinaceous factor was responsible for this activity. The removal of glutathione-S-transferase (GST) from tick salivary glands extracts (SGE) showed that this B-cell inhibitory protein (BIP) was not a GST. Gel filtration liquid chromatography indicated that BIP has a native molecular weight of approximately 18,000. An enrichment protocol, using a combination of anion-exchange and reverse-phase liquid chromatography, was established. BIP-enriched fractions did not suppress T-cell proliferation. Delayed addition of BIP-enriched fractions, up to 7 hr after LPS addition, inhibited the proliferation of isolated B cells. BIP-enriched fractions dramatically inhibited both OspA- and OspC-induced proliferation of isolated B cells. These results strongly suggest that BIP may facilitate B. burgdorferi transmission by preventing B-cell activation, and also highlights the potential of BIP as a therapeutic agent in B-cell maladies.
Hannier
Sigrid
S
School of Biological Science, Zoology, University of Aberdeen, UK.
Liversidge
Janet
J
Sternberg
Jeremy M
JM
Bowman
Alan S
AS
D000818:Animals; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors; D001428:Bacterial Vaccines; D025065:Borrelia burgdorferi; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D003208:Concanavalin A / Q000276:immunology; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D018884:Ixodes / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008074:Lipoproteins / Q000037:antagonists & inhibitors; D008193:Lyme Disease / Q000276:immunology / Q000635:transmission*; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D008970:Molecular Weight; D012463:Saliva / Q000276:immunology*; D013154:Spleen / Q000276:immunology
D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D008070:Lipopolysaccharides; D008074:Lipoproteins; D008222:Lymphokines; C072045:OspA protein; C079616:OspC protein; D003208:Concanavalin A