Abnormal b-cell subset and blimp-1-mediated humoral responses associated with visceral leishmaniasis pathogenesis

Abstract

B-cells have a spectrum of functions ranging from antibody production to antigen presentation and have additional vital roles in immune mechanisms. There is rudimentary knowledge about the role of B-cells in intracellular infections with contradictory findings. We explored the role of B-cell dysfunctions in visceral leishmaniasis (VL) pathogenesis in terms of the phenotypic and functional properties of B-cells during the course of disease. This study was performed on blood and splenic aspirates (SA) of VL cases pre- and post-treatment. Whole blood was used for flow cytometric studies for determining the profiles of B-cells at different time-points of treatment. Peripheral blood mononuclear cells were used for magnetic purification of B-cells, for transcriptional studies by real-time polymerase chain reaction (RT-PCR). Serum/plasma was used for direct agglutination test for determining parasite-specific antibodies and SAwere usedfor scoringthepresence ofparasitebymicroscopic examination. Flowcytometric studiesdepicteddecreased B-cell percentages during the entire course of disease and attainment of exhaustive phenotypewith tissue-likememory cell markers, indicative of B-cell dysfunctions in VL. In addition, B-cells had compromised abilities of antigen processing and presentation and altered levels of B-lymphocyte-induced maturation protein-1 (Blimp-1). Blimp-1 expression goes hand in hand with B-cell maturation antigen and transmembrane activator and calcium modulator (TACI) and cyclophilin ligand interactor, suggestive of its role in promoting plasma cell survival and antibody production. Elevated level of VL-specific antibody titre was directly correlated with exhausted phenotype and also with disease severity during VL. This study indicated for impaired B-cell functions during chronic infection which may lead to pathological consequences in human VL.