The role of the BAFF/APRIL system in the T cell-independent specific response to blood stage Plasmodium falciparum hemozoin
| Autor: | Surachet Benjathummarak, Wilanee Dechkajorn, Ratchanok Kumsiri, Yaowapa Maneerat |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Hemeproteins Adolescent T cell T-Lymphocytes Transmembrane Activator and CAML Interactor Protein Immunology Naive B cell Plasmodium falciparum Tumor Necrosis Factor Ligand Superfamily Member 13 Lymphocyte Activation Biochemistry Monocytes 03 medical and health sciences Young Adult 0302 clinical medicine B-Cell Activating Factor medicine Immunology and Allergy Humans RNA Messenger BAFF receptor B-cell activating factor Receptor Molecular Biology B cell B-Lymphocytes Chemistry B-Cell Maturation Antigen Monocyte Hematology Middle Aged Molecular biology Coculture Techniques 030104 developmental biology medicine.anatomical_structure Immunoglobulin G Interleukin-4 030215 immunology Signal Transduction |
| Zdroj: | Cytokine. 111 |
| ISSN: | 1096-0023 |
| Popis: | Background The B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are tumor necrosis factor family members that regulate B cell maturation, proliferation, survival and function. We have previously shown that blood-stage Plasmodium falciparum hemozoin (HZ) can act as a T-independent antigen (TI Ag) that induces the production of specific IgG to soluble crude P. falciparum Ag through the BAFF pathway. However, we have not yet clarified whether HZ need APRIL signaling in the TI response. Here, we aimed to clarify whether both BAFF and APRIL signaling pathways play roles in HZ induction of specific antibody production without T-cell help. Methods Normal monocytes alone or co-cultured with naive B cells were stimulated by HZ (10 µM) in vitro. Naive B cell cultures, with HZ alone or with exogenous recombinant BAFF (rBAFF) and recombinant APRIL (rAPRIL) plus recombinant IL-4 (rIL-4) for 6 and 10 days were used as controls to investigate activation of B cells. At various times, the levels of sBAFF, sAPRIL, and HZ-specific IgG in the culture supernatants were assessed by enzyme-linked immunosorbent assay. The BAFF and APRIL expression levels on the HZ-stimulated monocytes and their specific receptors on activated B cells, including the BAFF receptor (BAFF-R), the transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) and the B cell maturation antigen (BCMA), were determined by flow cytometry. mRNA expression levels for the receptors were validated using Real-Time quantitative PCR. Results HZ-activated monocytes released sBAFF and sAPRIL during the 72 h stimulation period. Increased mRNA encoding of their cognate receptors, BAFF-R, TACI, and BCMA, and increased HZ-specific IgG levels were also observed in HZ induction within the monocyte and B cell co-culture. The experiments under control conditions revealed that HZ alone could induce B cell culture to produce a small amount of the specific IgG compared with those in medium alone or rBAFF + rAPRIL + rIL-4. Conclusion Taken together, we suggest that in the TI response HZ stimulates monocyte and B cell co-culture to produce specific IgG through BAFF, APRIL and other independent complimentary signaling pathways. |
| Databáze: | OpenAIRE |
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