Open AccessTransgelin-2 is upregulated on activated B-cells and expressed in hyperplastic follicles in lupus erythematosus patients
Author(s) -
Kaori Kiso,
Hajime Yoshifuji,
Teruo Oku,
Masaki Hara,
Koji Kitagori,
Yoshitaka Hirayama,
Toshiki Nakajima,
Hironori Haga,
Tatsuaki Tsuruyama,
Aya MiyagawaHayashino
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0184738
Subject(s) - biology , germinal center , gene knockdown , downregulation and upregulation , cd19 , microbiology and biotechnology , b cell , cell culture , flow cytometry , immunology , antibody , genetics , gene , biochemistry
Transgelin-2 (TAGLN2) is an actin-binding protein that controls actin stability and promotes T cell activation. TAGLN2 is also expressed on B-cells but its function in B-cells is unknown. We found that TAGLN2-expressing B-cells were localized in the germinal center (GC) of secondary lymphoid tissues and TAGLN2 mRNA was significantly upregulated after IgM+IgG stimulation in primary human B-cells, suggesting that TAGLN2 was upregulated upon B-cell activation. In support of this, lymph nodes (LNs) from patients with systemic lupus erythematosus (SLE), in which the intense GC activity have been recognized, showed increased TAGLN2 expression in B-cells compared to control LNs. Moreover, TAGLN2 + B-cells were distributed widely not only in the GC but also in the perifollicular areas in SLE LNs. In contrast, CD19 + B-cells and CD19 + CD27 + memory-B cells in peripheral blood of SLE patients showed no increase in TAGLN2 mRNA. Two-photon excitation microscopy of Raji cells demonstrated that TAGLN2 colocalized with F-actin and moved together to the periphery upon stimulation. TAGLN2 -knockdown in Raji cells resulted in impaired phosphorylation of PLCγ2 leading to inhibition of cell migration. Microarray analysis of TAGLN2 -knockdown Raji cells showed decreased expression of the genes associated with immune function including CCR6 and as well as of those associated with regulation of the actin cytoskeleton including ABI2 , compared to controls. These results suggest that TAGLN2 might regulate activation and migration of B-cells, in particular, the entry of activated B-cells into the follicle. We also suggest that TAGLN2 could be used as a marker for activated B-cells.