Exogenous and endogenous TLR ligands activate anti-chromatin and polyreactive B cells.
Autoreactive B cells may become activated in a T-independent manner via synergistic engagement of the BCR and TLRs. Using the VH3H9 Ig H chain transgene to track anti-chromatin B cells, we demonstrate that VH3H9/Vlambda1 anti-chromatin B cells proliferate in response to stimulatory oligodeoxynucleotides containing CpG motifs, suggesting that these autoreactive B cells are responsive to TLR9 signaling. Strikingly, some VH3H9 B cells, but not the well-characterized VH3H9/Vlambda1 B cells, proliferate spontaneously in culture medium. This proliferation is blocked by inhibitory CpG oligodeoxynucleotides, implicating the TLR9 (or possibly TLR7) pathway. Most hybridomas generated from the proliferating cells are polyreactive, and one exhibits binding to nuclear Ags but not to the other Ags tested. Thus, B cells carrying autoreactive and/or polyreactive specificities may be susceptible to T cell-independent activation via dual engagement of the BCR and TLRs.
Fields
Michele L
ML
The Wistar Institute, Philadelphia, PA 19104, USA.
Metzgar
Michele H
MH
Hondowicz
Brian D
BD
Kang
Sun-Ah
SA
Alexander
Shawn T
ST
Hazard
Kristin D
KD
Hsu
Alice C
AC
Du
Yang-Zhu
YZ
Prak
Eline Luning
EL
Monestier
Marc
M
Erikson
Jan
J
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000502:physiology; D000818:Animals; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000096:biosynthesis*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002843:Chromatin / Q000276:immunology*; D018899:CpG Islands / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D009838:Oligodeoxyribonucleotides / Q000378:metabolism / Q000494:pharmacology; D051217:Toll-Like Receptor 9 / Q000378:metabolism* / Q000502:physiology
D000276:Adjuvants, Immunologic; D001323:Autoantibodies; C408982:CPG-oligonucleotide; D002843:Chromatin; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9