Blood stage Plasmodium falciparum antigens induce T cell independent immunoglobulin production via B cell activation factor of the TNF family (BAFF) pathway

Abstract

T independent (TI) antigens (Ags) activate monocytes to produce a cytokine, termed B cell activation factor (BAFF), involved in immunoglobulin (Ig) production. This study aimed to investigate whether the soluble schizont fraction of Plasmodium falciparum antigen (sPfAg) and hemozoin (HZ) could act as TI Ag to induce P. falciparum (Pf) specific Ig production via BAFF pathway. Co-cultures of monocytes and naïve B cells from 6 healthy donors were stimulated with sPfAg (10 mg/ml) or HZ (10 μM). At interval times, the expressions of BAFF on activated monocytes, BAFF receptor (BAFF-R) and proliferation nuclear Ag in activated B cells were determined by flow cytometry. The soluble BAFF (sBAFF), total and specific IgG levels in the supernatants were assessed by enzyme-linked immunosorbent assay (ELISA). The finding revealed both sPfAg and HZ could activate monocytes to express BAFF on surface and release sBAFF in the supernatant within 72 h of stimulation. The B cells responded to specific activation, indicated by BAFF-R expression on the surface within 72 h, marked proliferation on day 7, and final production of total and specific IgG during days 7–12. Comparing to sPfAg, HZ stimulated monocyte and B cell co-culture to express higher levels of BAFF and sBAFF during 24–48 h, more BAFF-R on HZ activated B cells within 24 h and induced marked proliferation of B cells with higher Pf specific IgG level. However, stimulation with sPfAg showed a more significant correlation between BAFF expression on the activated monocytes at 72 h and the Pf specific IgG level on day 12 ( r = 0.961, p = 0.039, Pearson Correlation). In conclusion, it is possible that both sPfAg and HZ stimulated B cells to produce specific IgG with BAFF involvement.