1. Atypical B cells up-regulate costimulatory molecules during malaria and secrete antibodies with T follicular helper cell support.
- Author
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Hopp CS, Skinner J, Anzick SL, Tipton CM, Peterson ME, Li S, Doumbo S, Kayentao K, Ongoiba A, Martens C, Traore B, and Crompton PD
- Subjects
- Humans, Immunoglobulin M, Immunologic Memory, Plasmodium falciparum, T Follicular Helper Cells, Influenza, Human, Malaria
- Abstract
Several infectious and autoimmune diseases are associated with an expansion of CD21
- CD27- atypical B cells (atBCs) that up-regulate inhibitory receptors and exhibit altered B cell receptor (BCR) signaling. The function of atBCs remains unclear, and few studies have investigated the biology of pathogen-specific atBCs during acute infection. Here, we performed longitudinal flow cytometry analyses and RNA sequencing of Plasmodium falciparum ( Pf )-specific B cells isolated from study participants before and shortly after febrile malaria, with simultaneous analysis of influenza hemagglutinin (HA)-specific B cells as a comparator. At the healthy baseline before the malaria season, individuals had similar frequencies of Pf - and HA-specific atBCs that did not differ proportionally from atBCs within the total B cell population. BCR sequencing identified clonal relationships between Pf -specific atBCs, activated B cells (actBCs), and classical memory B cells (MBCs) and revealed comparable degrees of somatic hypermutation. At the healthy baseline, Pf -specific atBCs were transcriptionally distinct from Pf -specific actBCs and classical MBCs. In response to acute febrile malaria, Pf -specific atBCs and actBCs up-regulated similar intracellular signaling cascades. Pf -specific atBCs showed activation of pathways involved in differentiation into antibody-secreting cells and up-regulation of molecules that mediate B-T cell interactions, suggesting that atBCs respond to T follicular helper (TFH ) cells. In the presence of TFH cells and staphylococcal enterotoxin B, atBCs of malaria-exposed individuals differentiated into CD38+ antibody-secreting cells in vitro, suggesting that atBCs may actively contribute to humoral immunity to infectious pathogens.- Published
- 2022
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