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
Cell Reports | CELL PRESS | Published : 2019
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 avid..View full abstract
We thank Prof. Di Yu for scientific advice. This work was supported by the Australian Government National Health and Medical Research Council Independent Research Institute Infrastructure Support Scheme (IRIISS) and project grants 1058665 and 1137989, the Australian Academy of Science (D.S.H.), fellowships from the Sylvia and Charles Viertel Foundation, the National Health and Medical Research Council and Commonwealth Serum Laboratory (A.K., K.L.G.-J., and W.S.), and the Victorian State Government Operational Infrastructure Support.