Sustained secretion of immunoglobulin by long-lived plasma cells from human nasal biopsies

Abstract

Abstract Background During secondary immune responses, plasma cell survival and antibody production is mediated by extrinsic factors provided by the local environment. It is unknown whether there are long-lived plasma cells (LLPCs) in the human nasal mucosa. Objective To identify LLPCs and characterize functionally specific survival niche in the human nasal mucosa. Methods Nasal polyp (NP) biopsies were used for ex vivo air-liquid interface culture. Protein levels of immunoglobulins in tissue homogenates were detected by Bio-Plex. The expression of LLPCs related markers including NGF, TrkA, P75, IL-6, APRIL, CD138, CD20, CD4, CD8, ECP, Bcl2, Ki-67, CD3 were detected by means of quantitative RT-PCR, immunohistochemistry (IHC) and ELISA. Results Using an ex vivo biopsies culture, we found sustained IgG, IgA, IgE, and IgM secretion >4 wk of culture. IL-6, APRIL NGF, TrkA, and P-75 were up-regulated in CRSwNP compared with controls by ELISA or IHC. We assessed TrkA+ cells, ECP+ eosinophils, and tryptase+ mast cells represent the major interstitial cell sources of NGF, while tryptase+ mast cells and CD138+ plasma cells represent the major sources for TrkA in CRSwNP by immunohistochemistry. We performed histological analysis of fresh nasal polyp tissues, and of tissue fragments harvested 10, 20, 32 days after cultured respectively and found that there’s a small portion of plasma cell in CRSwNP expressed Bcl2 pre- and post-culture. However, post-cultured plasma cells do not express Ki67. Conclusion This study demonstrates that the human nasal mucosa harbors a population of nonproliferating plasma cells that are instructed by the microenvironment for prolonged survival and Ab secretion.