The Role Of Transcription Factor T-Bet In B Cell Mediated Responses To Plasmodium Infection

Abstract Malaria is a global health concern which affects over 200 million individuals worldwide. Although the immune system rapidly responds to Plasmodium infection with specific antibodies, natural antibodies fail to establish long term protection, often leading to repetitive infections and chronicity. Recent studies showed that in a chronic malaria setting both B cells and T cells induce expression of T-bet transcription factor. It is not completely understood whether this is a part of the specific host defense or a result of disease pathogenesis. Here using transgenic mouse models, we show that knockout of T-bet or IFN-g similarly reduces survival of mice compared to WT upon infection with Plasmodium chabaudi, therefore suggesting a protective role for T-bet. To determine the specific role T-bet plays in B cell responses to Plasmodium, we first identified that T-bet expression in mouse B cells are triggered by dual stimulation of IFN-g and B cell receptor. Similarly using Tbet-zsgreen transgenic mice we showed that conditions specific to Plasmodium chabaudi infection drive T-bet expression in multiple B cell subsets in a time dependent fashion. However, no such induction is shown when mice are immunized with T-dependent protein antigens adjuvanted with Alum. On the other hand, bone marrow chimeric animals reconstituted with equal amounts of congenically labeled WT and T-bet KO bone marrow cells showed that for most B cell subsets the lack of T-bet does not change the ratio of WT and KO cells upon Plasmodium infection indicating that T-bet expression may not be equally critical for all B cell responses to infection. These findings suggest a complex role of T-bet in the development of humoral responses.