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Cell Rep. 2019 Nov 19;29(8):2257-2269.e6. doi: 10.1016/j.celrep.2019.10.087.

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

Author information

1
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
2
The University of Melbourne, Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth Street, Melbourne, Victoria 3000, Australia.
3
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia; Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
4
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia; Department of Computing and Information Systems, The University of Melbourne, Parkville, Victoria 3010, Australia.
5
The University of Melbourne, Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth Street, Melbourne, Victoria 3000, Australia. Electronic address: axel.kallies@unimelb.edu.au.
6
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address: hansen@wehi.edu.au.

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.

KEYWORDS:

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

PMID:
31747599
DOI:
10.1016/j.celrep.2019.10.087
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