TLR9 drives the development of transitional B cells towards the marginal zone pathway and promotes autoimmunity.
Maturation of B cells depends on environmental stimuli. Peripheral immature B cells develop into follicular pathway when antigenic stimulation is combined with T cell signals. Here, we wished to identify stimuli contributing to the development into marginal zone B cells known to be involved in autoimmune response. We found that TLR9 stimulation of transitional B cells induces proliferation and specific maturation into CD24(-) CD38(+) CD21(high) CD23(low) IgM(high) IgD(low) and Notch2(high) B cells characteristics of marginal zone B cells. Terminal differentiation into antibody-secreting cell associated with isotype switch commitment is also triggered which leads to a striking production of autoantibodies. Interestingly, mature B cells do not differentiate into marginal zone pathway following TLR9 stimulation, nor do transitional B cells under antigenic and T cell combined signals. These results suggest that transitional B cells are specifically sensitive to TLR9 stimulation to produce autoreactive marginal zone B cells.
EA2216 Immunologie et Pathologie, IFR148 ScInBioS, Université de Brest et Université Européenne de Bretagne, Brest, France.
Thomas
T
Guerrier
Pierre
P
Youinou
Jacques-Olivier
JO
Pers
Christophe
C
Jamin
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000921:Antibody-Producing Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology; D015551:Autoimmunity; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D014066:Palatine Tonsil / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D001323:Autoantibodies; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9