Abstract
Ectopic lymphoid tissues (eLTs) characterized by B cell aggregation contribute to the local immunoglobulin production in nasal polyps (NPs). B cell-activating factor (BAFF) is vital for B cell survival, proliferation, and maturation. The purpose of this study is to investigate whether BAFF is involved in the B cell survival and eLT formation in NPs. The mRNA and protein levels of BAFF in NP tissues with and without eLTs were detected by PCR and ELISA assay, respectively. The cellular sources of BAFF and active caspase-3-positive B cells in NPs were studied by immunofluorescence staining. B cells purified from NP tissues were stimulated with BAFF and were analyzed by flow cytometry. Stromal cells purified from NP tissues were stimulated with lymphotoxin (LT) α1β2, and BAFF levels in culture supernatants were analyzed by ELISA. Compared with those in control tissues and NPs without eLTs, the BAFF levels were elevated in NPs with eLTs. Abundant BAFF-positive cells and few active caspase-3-positive apoptotic B cells were found in NPs with eLTs, in contrast to those in NPs without eLTs. There was a negative correlation between the numbers of BAFF-positive cells and frequencies of apoptotic B cells in total B cells in NP tissues. BAFF protected nasal polyp B cells from apoptosis in vitro. Stromal cells were an important cellular source of BAFF in NPs with eLTs. LTα1β2 induced BAFF production from nasal stromal cells in vitro. We propose that BAFF contribute to eLT formation in NPs by promoting B cell survival.
Highlights
Nasal polyps (NPs) are characterized by persistent inflammation of nasal and paranasal sinus mucosa with the presence of edematous outgrowth [1]
Consistent with previous studies [21,22,23], we found that compared to those in control tissues, BAFF levels were elevated in both NP tissues with and without ectopic lymphoid tissues (eLTs) at the mRNA and protein level detected by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) assays, respectively, there was a further increase of BAFF
To explore whether increased BAFF has a role in B cell survival in NPs with eLTs, we studied the relationship between BAFF+ cells and active caspase-3+CD20+ apoptotic B cells in NP tissues
Summary
Nasal polyps (NPs) are characterized by persistent inflammation of nasal and paranasal sinus mucosa with the presence of edematous outgrowth [1]. Accumulating evidence suggest that local immunoglobulin (Ig) overproduction contributes to the local activation of mast cells, eosinophils, and complements, playing an important role in the pathogenesis of NPs and associating with the poor treatment outcomes [4, 5]. Several studies have identified the formation of ectopic lymphoid tissues (eLTs) in BAFF in NPs With eLTs. NPs and revealed a critical role of eLTs in supporting local immunoglobulin production in NPs [6,7,8,9,10]. Our recent study found that IL-17A-induced nasal stromal cell remodeling and crosstalk between B and stromal cells via B cell chemokine-C-X-C motif chemokine ligand 13 (CXCL13) and lymphotoxin (LT) a1b2 have an important role in B cell recruitment and the eLT formation in NPs [9]. Whether BAFF is involved in the survival of B cells and formation of eLTs in NPs is still an open question
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