Interferon-γ signal drives differentiation of T-bethi atypical memory B cells into plasma cells following Plasmodium vivax infection

For development of a long-lasting protective malaria vaccine, it is crucial to understand whether Plasmodium-induced memory B cells (MBCs) or plasma cells develop and stably contribute to protective immunity, or on the contrary the parasite suppresses antibody responses by inducing MBC dysfunction. The expansion of T-bet(hi) atypical MBCs is described in chronic Plasmodium falciparum-exposed individuals. However, it remains unclear whether accumulation of T-bet(hi) atypical MBCs is indicative of a protective role or rather an impaired function of the immune system in malaria. Here, the phenotypic and functional features of T-bet(hi) atypical MBCs were studied in P. vivax patients living in an area of low malaria transmission. During P. vivax infection, the patients produced a twofold higher frequency of T-bet(hi) atypical MBCs compared to malaria non-exposed individuals. This distinct atypical MBC subset had a switched IgG phenotype with overexpression of activation markers and FcRL5, and decreased Syk phosphorylation upon BCR stimulation. Post-infection, expansion of T-bet(hi) IgG(+) atypical MBCs was maintained for at least 3 months. Further studies of the contribution of T-bet(hi) atypical MBC function to humoral immunity showed that synergizing IFN-gamma with TLR7/8 and IL-21 signals was required for their differentiation into plasma cells and antibody secretion.

Automated summary

The study investigated the phenotypic and functional features of T-bet(hi) atypical MBCs in P. vivax patients living in an area of low malaria transmission. It was found that these atypical MBCs showed a distinct IgG phenotype with increased activation markers and FcRL5 expression, and decreased Syk phosphorylation upon BCR stimulation. The expansion of T-bet(hi) IgG(+) atypical MBCs was maintained for at least 3 months post-infection, and further research suggested that synergizing IFN-gamma with TLR7/8 and IL-21 signals was necessary for their differentiation into plasma cells and antibody secretion.