BOB.1 controls memory B-cell fate in the germinal center reaction

Maartje J. Levels, Cynthia M. Fehres, Lisa G. M. van Baarsen, Nathalie O. P. van Uden, Kristine Germar, Tom G. O'Toole, Iris C. J. Blijdorp, Johanna F. Semmelink, Marieke E. Doorenspleet, Arjen Q. Bakker, Mikhail Krasavin, Alexey Tomilin, Sophie Brouard, Hergen Spits, Dominique L. P. Baeten, Nataliya G. Yeremenko

    Research output

    Abstract

    During T cell-dependent (TD) germinal center (GC) responses, naive B cells are instructed to differentiate towards GC B cells (GCBC), high-affinity long-lived plasma cells (LLPC) or memory B cells (Bmem). Alterations in the B cell-fate choice could contribute to immune dysregulation leading to the loss of self-tolerance and the initiation of autoimmune disease. Here we show that mRNA levels of the transcription regulator BOB.1 are increased in the lymph node compartment of patients with rheumatoid arthritis (RA), a prototypical auto immune disease caused by the loss of immunological tolerance. Investigating to what extent levels of BOB.1 impact B cells during TD immune responses we found that BOB.1 has a crucial role in determining the B cell-fate decision. High BOB.1 levels promote the generation of cells with phenotypic and functional characteristics of Bmem. Mechanistically, overexpression of BOB.1 drives ABFI and suppresses BCL6, favouring Bmem over LLPC or recycling GCBC. Low levels of BOB.1 are sufficient for LLPC but not for Bmem differentiation. Our findings demonstrate a novel role for BOB.1 in B cells during TD GC responses and suggest that its dysregulation may contribute to the pathogenesis of RA by disturbing the B cell-fate determination.

    Original languageEnglish
    Pages (from-to)131-144
    JournalJournal of Autoimmunity
    Volume101
    Early online date30 Apr 2019
    DOIs
    Publication statusPublished - Jul 2019

    Cite this

    Levels, M. J., Fehres, C. M., van Baarsen, L. G. M., van Uden, N. O. P., Germar, K., O'Toole, T. G., Blijdorp, I. C. J., Semmelink, J. F., Doorenspleet, M. E., Bakker, A. Q., Krasavin, M., Tomilin, A., Brouard, S., Spits, H., Baeten, D. L. P., & Yeremenko, N. G. (2019). BOB.1 controls memory B-cell fate in the germinal center reaction. Journal of Autoimmunity, 101, 131-144. https://doi.org/10.1016/j.jaut.2019.04.011