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=11

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=<p>We have previously shown that a variant of the <italic>TNFSF13B</italic> gene that we called <italic>BAFF-var</italic> increases the production of the cytokine BAFF, upregulating humoral immunity and increasing the risk for certain autoimmune diseases. In addition, genetic population signatures revealed that <italic>BAFF-var</italic> 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 experimentally assessed the role of <italic>BAFF-var</italic> in response to malaria antigens. Lysates of erythrocytes infected with <italic>Plasmodium falciparum</italic> (iRBCs) or left uninfected (uRBCs, control) were used to treat peripheral blood mononuclear cells (PBMCs) with distinct BAFF genotypes. The PBMCs purified from <italic>BAFF-var</italic> donors and treated with iRBCs showed different levels of specific cells, immunoglobulins, and cytokines as compared with <italic>BAFF-WT.</italic> In particular, 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 <italic>BAFF-var</italic> may have improved fitness during <italic>P. falciparum</italic> infection.</p>