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TLR9 drives the development of transitional B cells towards the marginal zone pathway and promotes autoimmunity

Thomas Guerrier1, Pierre Youinou, Jacques-Olivier Pers

  • 1EA2216 Immunologie et Pathologie, IFR148 ScInBioS, Université de Brest et Université Européenne de Bretagne, Brest, France.

Journal of Autoimmunity
|June 15, 2012
PubMed

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.

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