TLR-mediated loss of CD62L focuses B cell traffic to the spleen during Salmonella typhimurium infection.
B cells recognize Ags on microorganisms both with their BCRs and TLRs. This innate recognition has the potential to alter the behavior of whole populations of B cells. We show in this study that in culture and in mice, MyD88-dependent activation of B cells via TLR2 or TLR9 causes the rapid loss of expression of CD62L by metalloproteinase-dependent shedding. Adoptive transfer of in vitro CpG-activated B cells showed them to be excluded from lymph nodes and Peyer's patches, but not the spleen. In vivo, both injection of CpG and systemic infection with Salmonella typhimurium caused the shedding of CD62L and the consequent focusing of B cell migration to the spleen and away from lymph nodes. We propose that wholesale TLR-mediated changes to B cell migration influence the development of immunity to pathogens carrying appropriate ligands.
Morrison
Vicky L
VL
School of Biological Sciences, Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom.
Barr
Tom A
TA
Brown
Sheila
S
Gray
David
D
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology* / Q000637:transplantation; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D019041:L-Selectin / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008024:Ligands; D055666:Lipopeptides / Q000008:administration & dosage / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D045726:Metalloproteases; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000502:physiology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000378:metabolism; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D012486:Salmonella typhimurium / Q000276:immunology; D013154:Spleen / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D051217:Toll-Like Receptor 9 / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*
C408982:CPG-oligonucleotide; D008024:Ligands; D055666:Lipopeptides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D009838:Oligodeoxyribonucleotides; C508075:Pam(3)CSK(4) peptide; C493486:Tlr2 protein, mouse; C495370:Tlr9 protein, mouse; D051195:Toll-Like Receptor 2; D051217:Toll-Like Receptor 9; D019041:L-Selectin; D045726:Metalloproteases