GSE120728 Transcription factor T-bet in B cells controls germinal centre polarization and antibody affinity maturation in response to malaria (RNA-seq)

Contributors : Ann Ly ; Yang Liao ; Halina Pietrzak ; Lisa J Ioannidis ; Tom Sidwell ; Renee Gloury ; Anthony Triglia ; Kim Good-Jacobson ; Wei Shi ; Axel Kallies ; Diana S HansenSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusDespite the key role that antibodies play in protection against malaria, the cellular processes modulating the acquisition of immunity are not fully understood. Using an infection model of severe malaria, we found that GC B cells strongly upregulate the transcription factor T-bet in response to infection. Expression of T-bet in B cells was required for IgG2c switching but reduced the magnitude of GC B cell responses. RNA-sequencing and flow cytometry analysis revealed that T-bet supports a transcriptional program resulting in a substantial enrichment of the GC dark zone (DZ), thereby significantly influencing DZ/light zone (LZ) polarization. Mice deficient in T-bet in their B cells displayed significantly reduced affinity mutation frequencies in their IghV genes and lower antibody avidity than controls, indicating that T-bet modulates affinity maturation. These results demonstrate that T-bet promotes appropriate GC dynamics, thereby leading to the differentiation of B cells with increased affinity for antigen.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research