previous studies have reported activation of the B cell-activating factor (BAff)/a proliferation-inducing ligand (ApRiL) system in t independent immunity against malaria infection. Plasmodium falciparum (P. falciparum) infected animal model is not feasible. therefore, little is known about the occurrence of BAff/ApRiL system and changes in falciparum lymphoid tissues. this study aimed to investigate the expression of BAff/ApRiL system components in lymphoid tissues from P. falciparum infected patients. Spleen and lymph node samples from 14 patients were collected at autopsy. Normal spleens and bacterially infected tonsils served as controls. the protein and/or mRnA expression of BAff/ApRiL and their cognate receptors, BAff-R, tAci and BcMA, were determined by immunohistochemistry and Rt-qPCR, respectively. The spleens of the patients exhibited significantly higher BAFF-R protein expression than normal spleens. Although without appropriate control, BcMA protein was markedly observed only in the lymph nodes. BAFF and BCMA mRNA levels were also significantly elevated in the spleen tissues of the patients compared with normal spleens. the overall BAff-R protein levels in the lymphoid tissues of the patients correlated positively with parasitaemia. These findings are the first to confirm that BAFF/ ApRiL system activation in lymphoid tissues and is positively correlated with the parasitaemia levels in falciparum malaria. The B cell-activating factor (BAFF)/a proliferation-inducing ligand (APRIL) system consists of BAFF, APRIL, and three cognate receptors expressed on B cells: B cell maturation antigen (BCMA), transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) 1 , and BAFF receptor (BAFF-R) 2-4. The BAFF/ APRIL system plays multiple regulatory roles in the T cell independent (TI) immune response, including B cell activation, homeostasis, and survival 5. APRIL binds with high affinity to both BCMA and TACI, while BAFF has lower affinity for these receptors and binds mainly to BAFF-R (reviewed in Dillon et al. 6). Ligand binding triggers activation of diverse signalling pathways, including the mitogen-activated kinase and nuclear factor-κB pathways 7,8 to induced immunoglobulin heavy chain class-switch recombination (CSR), and IgG and IgA production by B cells 5. BAFF and APRIL are predominantly expressed by myeloid cells such as monocytes, macrophages, and dendritic cells 9 and can be induced or upregulated by cytokines such as interferon-α and-γ, transforming growth factor-β, interleukin-4 and −10 2,10,11. Spleen and lymph nodes play pivotal roles in the host response to malaria. For example, the spleen eliminates Plasmodium parasitised red blood cells (PRBCs), and immune cells in both organs produce effector cytokines and specific anti-malaria antibodies that promote clearance of infection 12,13. The BAFF/APRIL system plays well-characterised roles in numerous human disorders, including autoimmune diseases 14-19 , cancers 20 , and bacterial 21 , viral 22 , and fungal 23 infections. ...