Scientific Reports (Mar 2022)

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

  • Piyawan Kochayoo,
  • Pongsakorn Thawornpan,
  • Kittikorn Wangriatisak,
  • Siriruk Changrob,
  • Chaniya Leepiyasakulchai,
  • Ladawan Khowawisetsut,
  • John H. Adams,
  • Patchanee Chootong

DOI
https://doi.org/10.1038/s41598-022-08976-6
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 11

Abstract

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Abstract 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-bethi atypical MBCs is described in chronic Plasmodium falciparum-exposed individuals. However, it remains unclear whether accumulation of T-bethi 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-bethi 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-bethi 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-bethi IgG+ atypical MBCs was maintained for at least 3 months. Further studies of the contribution of T-bethi atypical MBC function to humoral immunity showed that synergizing IFN-γ with TLR7/8 and IL-21 signals was required for their differentiation into plasma cells and antibody secretion.