title: High levels of circulating triiodothyronine induce plasma cell differentiation.
abstract: The effects of hyperthyroidism on B-cell physiology are still poorly known. In this study, we evaluated the influence of high-circulating levels of 3,5,3'-triiodothyronine (T3) on bone marrow, blood, and spleen B-cell subsets, more specifically on B-cell differentiation into plasma cells, in C57BL/6 mice receiving daily injections of T3 for 14 days. As analyzed by flow cytometry, T3-treated mice exhibited increased frequencies of pre-B and immature B-cells and decreased percentages of mature B-cells in the bone marrow, accompanied by an increased frequency of blood B-cells, splenic newly formed B-cells, and total CD19(+)B-cells. T3 administration also promoted an increase in the size and cellularity of the spleen as well as in the white pulp areas of the organ, as evidenced by histological analyses. In addition, a decreased frequency of splenic B220(+) cells correlating with an increased percentage of CD138(+) plasma cells was observed in the spleen and bone marrow of T3-treated mice. Using enzyme-linked immunospot assay, an increased number of splenic immunoglobulin-secreting B-cells from T3-treated mice was detected ex vivo. Similar results were observed in mice immunized with hen egg lysozyme and aluminum adjuvant alone or together with treatment with T3. In conclusion, we provide evidence that high-circulating levels of T3 stimulate plasma cytogenesis favoring an increase in plasma cells in the bone marrow, a long-lived plasma cell survival niche. These findings indicate that a stimulatory effect on plasma cell differentiation could occur in untreated patients with Graves' disease.
authors.affiliation: Laboratory of Immunophysiology, Institute of Biomedical Sciences Institute of Biophysics Carlos Chagas Filho, Institute of Microbiology Paulo de Góes Institute of Medical Biochemistry, Federal University of Rio de Janeiro/UFRJ, Health Sciences Building, Av. Carlos Chagas Filho 373, Rio de Janeiro 21941-902, Brazil Institute of Biology, Fluminense Federal University, Niterói, Rio de Janeiro 24210-150, Brazil National Institute on Aging, NIH, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA.
authors.forename: Flavia Fonseca
authors.initials: FF
authors.lastname: Bloise
authors.forename: Felipe Leite de
authors.initials: FL
authors.lastname: Oliveira
authors.forename: Alberto Félix
authors.initials: AF
authors.lastname: Nobrega
authors.forename: Rita
authors.initials: R
authors.lastname: Vasconcellos
authors.forename: Aline
authors.initials: A
authors.lastname: Cordeiro
authors.forename: Luciana Souza de
authors.initials: LS
authors.lastname: Paiva
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Taub
authors.forename: Radovan
authors.initials: R
authors.lastname: Borojevic
authors.forename: Carmen Cabanelas
authors.initials: CC
authors.lastname: Pazos-Moura
authors.forename: Valéria de
authors.initials: Vd
authors.lastname: Mello-Coelho
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000097:blood / Q000503:physiopathology*; D007136:Immunoglobulins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010950:Plasma Cells / Q000166:cytology* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood* / Q000378:metabolism
chemical_list: D007136:Immunoglobulins; D014284:Triiodothyronine; D013974:Thyroxine
keywords: B lymphocyte; bone marrow; hyperthyroidism; plasma cell; spleen; thyroid hormone