Plasmodium-specific atypical memory B cells upregulate markers of activation and co-stimulatory molecules indicative of cellular interaction with T cells in response to a febrile malaria infection in children and adults.

ABSTRACT: In naturally acquired immunity to malaria, antibodies that reliably protect are only acquired after years of repeated Plasmodium falciparum (Pf) infections. We have shown in Mali that this inefficiency in humoral immunity to malaria is associated with a large expansion of CD21loCD27- ‘atypical’ B cells (atBCs). The function of atBCs remains elusive, as they exhibit altered B cell receptor (BCR) signaling and when activated fail to secrete cytokines and antibodies. We set out to study the participation and function of malaria-specific atBCs during the immune response to a febrile malaria infection. Here, we show in a Mali cohort spanning infants to adults, that atBCs frequencies within the malaria and influenza-specific MBC compartment are comparable to the overall atBC frequency, showing that atBCs are not predominantly expanded within Pf-specific B cells. We performed a transcriptional analysis of Pf- and influenza-specific atBCs, actBC and MBCs and show that CXCL16, IL-6, IL-10, TNFα, IL12R and IL12R are uniquely upregulated in Pf-specific atBCs. Comparative transcriptomic and flow cytometric analysis before and after an acute malaria infection showed that after malaria, Pf-specific atBCs are transcriptionally most like the actBC subset, sharing many common features, such as activation of intracellular signaling pathways and expression of high levels of T-bet, FcRL5, Ki67 and CD86. Unique to Pf-specific atBCs was an upregulation of IL-5RA, CD38, CXCR3, TLR7, 9 and 10 after a febrile malaria episode. Our data shows that atBCs exhibit a surface marker profile that could facilitate cellular interaction with T cells in secondary lymphoid tissues.

ORGANISM(S): Homo sapiens

PROVIDER: GSE183744 | GEO | 2022/06/01

REPOSITORIES: GEO