Transcription Factor T-bet in B Cells Modulates Germinal Center Polarization and Antibody Affinity Maturation in Response to Malaria

Ann Ly, Yang Liao, Halina Pietrzak, Lisa J. Ioannidis, Tom Sidwell, Renee Gloury, Marcel Doerflinger, Tony Triglia, Raymond Z. Qin, Joanna R. Groom, Gabrielle T. Belz, Kim L. Good-Jacobson, Wei Shi, Axel Kallies, Diana S. Hansen

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2 Citations (Scopus)

Abstract

Despite the key role that antibodies play in protection, the cellular processes mediating the acquisition of humoral immunity against malaria are not fully understood. Using an infection model of severe malaria, we find that germinal center (GC) B cells upregulate the transcription factor T-bet during infection. Molecular and cellular analyses reveal that T-bet in B cells is required not only for IgG2c switching but also favors commitment of B cells to the dark zone of the GC. T-bet was found to regulate the expression of Rgs13 and CXCR3, both of which contribute to the impaired GC polarization observed in the absence of T-bet, resulting in reduced IghV gene mutations and lower antibody avidity. These results demonstrate that T-bet modulates GC dynamics, thereby promoting the differentiation of B cells with increased affinity for antigen. Antibody responses play a pivotal role in clinical immunity to malaria. Ly et al. report that that germinal center (GC) B cells upregulate the transcription factor T-bet during infection. T-bet favors commitment of B cells to the GC dark zone, thereby augmenting immunoglobulin gene mutation rates and antibody affinity maturation.

Original languageEnglish
Pages (from-to)2257-2269
Number of pages13
JournalCell Reports
Volume29
Issue number8
DOIs
Publication statusPublished - 19 Nov 2019

Keywords

  • affinity maturation
  • antibodies
  • B cells
  • germinal center
  • malaria
  • T-bet

Cite this

Ly, A., Liao, Y., Pietrzak, H., Ioannidis, L. J., Sidwell, T., Gloury, R., Doerflinger, M., Triglia, T., Qin, R. Z., Groom, J. R., Belz, G. T., Good-Jacobson, K. L., Shi, W., Kallies, A., & Hansen, D. S. (2019). Transcription Factor T-bet in B Cells Modulates Germinal Center Polarization and Antibody Affinity Maturation in Response to Malaria. Cell Reports, 29(8), 2257-2269. https://doi.org/10.1016/j.celrep.2019.10.087