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Transcription Factor T-bet in B cells modulates germinal center polarization and antibody affinity maturation in response to malaria


Ly, A; Liao, Y; Pietrzak, H; Ioannidis, LJ; Sidwell, T; Gloury, R; Doerflinger, M; Triglia, T; Qin, RZ; Groom, JR; Belz, GT; Good-Jacobson, KL; Shi, W; Kallies, A; Hansen, DS
2019-11-19
Cell Reports
Journal Article
29
8
2257-2269 e6
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.
Elsevier
Infectious Diseases and Immune Defence; Bioinformatics; Immunology
10.1016/j.celrep.2019.10.087
31747599
Refer to article for additional funding acknowledgements
Refer to copyright notice on published article.

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Creation Date 2019-12-05 01:26:21 Last Modified 2020-02-11 09:03:26