Pluto Bioinformatics

GSE156102: Evolutionarily selected overexpression of the cytokine BAFF enhances mucosal immune response against P. falciparum

Bulk RNA sequencing

A variant of the TNFSF13B gene (BAFF-var) increases the production of the cytokine BAFF, up-regulating humoral immunity and increasing the risk for certain autoimmune diseases. BAFF-var was evolutionarily advantageous, most likely by increasing resistance to malaria infection. We assessed experimentally the role of BAFF-var in response to malaria antigens. Lysates of erythrocytes infected with Plasmodium falciparum (iRBCs) or left uninfected (uRBCs, control) were used to treat PBMCs with distinct BAFF genotypes. PBMCs purified from BAFF-var donors and treated with iRBCs showed different levels of specific cells, immunoglobulins and cytokines as compared with BAFF-WT. In particularly a relevant differential effect on mucosal immunity B subpopulations have been observed. RNA sequencing of total B cells, purified from PBMC treated with iRBCs or uRBCs, identified several transcripts differentially expressed including some that encoded proteins critical for the response to malaria infection. These findings point to specific immune cells and molecules through which the evolutionary selected BAFF-var may have improved fitness during P. falciparum infection. SOURCE: Supriyo DeComputational Biology & Genomics Core NIA-IRP, NIH

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