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Fig. 2 | Parasites & Vectors

Fig. 2

From: Regulation of immunity during visceral Leishmania infection

Fig. 2

Dysfunctional humoral response during visceral leishmaniasis. The picture summarizes the sequence of events that lead to a suboptimal humoral response during visceral leishmaniasis, based primarily on data from our recent study in non-human primates compounded with evidence from additional studies. (1) Shortly after parasite inoculation, B cells are activated in a non-specific manner by soluble parasite products that act as B cell mitogens as well as by inflammatory mediators generated during the response to infection. (2) As a result, B cells with the atypical CD21− CD27− phenotype expand and eventually give rise to plasmablasts that produce copious amounts of immunoglobulin leading to the occurrence of hypergammaglobulinemia. (3) Some B cells appear to be activated in a specific manner via their BCR and follow the follicular pathway where they engage in cognate interactions with pre-Tfh cells. (4) If these interactions are productive, both cell types proceed to form a germinal center where Tfh cells promote affinity maturation of B cell for their specific antigen and direct the selection of the B cells clones with the highest affinity. B cells then exit the germinal center as high-affinity CD27+ memory B cells and plasma cells that produce antibodies with high affinity for the parasite. (5) However, the germinal center response is not sustained during the chronic phase of infection accompanying the decreasing numbers of Tfh cells. A strong Th1-polarizing environment is established in the spleen during VL, with high levels of expression of T-bet in CD4 T cells. Given that T-bet and the Tfh master transcription factor, Bcl-6, mutually repress each other’s expression, it is reasonable to speculate that the inflammatory environment during VL is unfavourable for the sustained differentiation of Tfh cells

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