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

First Author  Ly A Year  2019
Journal  Cell Rep Volume  29
Issue  8 Pages  2257-2269.e6
PubMed ID  31747599 Mgi Jnum  J:298891
Mgi Id  MGI:6489035 Doi  10.1016/j.celrep.2019.10.087
Citation  Ly A, et al. (2019) Transcription Factor T-bet in B Cells Modulates Germinal Center Polarization and Antibody Affinity Maturation in Response to Malaria. Cell Rep 29(8):2257-2269.e6
abstractText  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.
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