Small molecule BCL6-inhibition suppresses follicular T helper cell differentiation and plasma blast formation

B cell responses are dependent on specialized help provided by follicular T helper (Tfh). Tfh and B cells both express the transcription factor B-cell lymphoma 6 protein (BCL6) and targeting BCL6 may thus prevent humoral allo-immune responses after transplantation. In this study, the effects of the small molecule BCL6 inhibitor 79-6 on human T and B cell differentiation and proliferation were investigated. To this end, naïve CD4 helper T cells and resting B cells were stimulated polyclonally in the presence of 79-6. This compound suppressed proliferation, differentiation, and function of Tfh cells, and also the proliferation and differentiation of B cells. Plasma blast formation was affected, resulting in inhibition of antibody production by > 70 % at the highest concentration of 79-6 used. A time-dependent impact of 79-6 on B cell functions was also demonstrated during allo-antigen stimulation. In contrast to the condition of adding 79-6 at day 0, addition on day 3 or 7 hardly inhibited plasma blast formation. In conclusion, targeting BCL6 with 79-6 inhibits T and B cells' differentiation towards Tfh cells and plasma blasts and subsequent antibody production. Small molecule 79-6 is a promising compound which might prevent interaction between Tfh and B cells.