AUTHOR=Lodde Valeria , Floris Matteo , Beerman Isabel , Munk Rachel , Guha Rajan , Steri Maristella , Orrù Valeria , Abdelmohsen Kotb , Crompton Peter D. , Gorospe Myriam , Idda Maria Laura , Cucca Francesco 

TITLE=Evolutionarily Selected Overexpression of the Cytokine BAFF Enhances Mucosal Immune Response Against P. falciparum

JOURNAL=Frontiers in Immunology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.575103

DOI=10.3389/fimmu.2020.575103

ISSN=1664-3224

ABSTRACT=We have previously shown that a variant of the TNFSF13B gene that we called BAFF-var, increases the production of the cytokine BAFF, up-regulating humoral immunity and increasing the risk for certain autoimmune diseases.  In addition, genetic population signatures revealed that BAFF-var was 
evolutionarily advantageous, most likely by increasing resistance to malaria infection which is a prime candidate for selective pressure.  To evaluate whether the increased soluble BAFF (sBAFF) production confers protection, 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 and B cells with distinct BAFF genotypes.  The 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.  These findings point to specific immune cells and molecules through which the evolutionary selected BAFF-var may have improved fitness during P. falciparum infection.