Bob1 limits cellular frequency of T follicular helper cells

T follicular helper (Tfh) cells are involved in specific humoral immunity at initial and recall phases. The fact that the transcription repressors Bcl-6 and Blimp-1 determine lineages of Tfh cells and other types of effector CD4⁺ T cells, respectively, suggests that there are unique mechanisms to establish Tfh-cell identity. In this study, we found that Tfh cells preferentially express the transcriptional coactivator Bob1. Bob1 of Tfh cells was dispensable for the expression of Bcl-6 and the functional property of the cells for B cell help. However, upon initial immunization of foreign antigens, the percentages of Tfh cells in Bob1^−/− mice were much higher than those in wild-type mice. In addition, expansion of Tfh cells within Bob1^−/−CD4⁺T cells transferred into wild-type mice revealed that the high frequency of Tfh cells was caused by a T-cell-intrinsic mechanism. These findings were further supported by the results of in vitro studies demonstrating that Bob1^−/− Tfh cells had greater proliferative activity in response to stimuli by CD3/CD28 monoclonal antibody (mAb) and were also refractory to CD3-induced cell death in comparison to wild-type Tfh cells. These results suggest that Tfh cells harbor a Bob1-related mechanism to restrict numerical frequency against stimulation of T-cell receptors.

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