Mechanisms of triiodothyronine on maturation and differentiation of B cells / 医学研究生学报

ABSTRACT

Objective Higher expression of B-cell activating factor (BAFF) in patients with Graves' disease can activate B cells and increase proportion of plasma cells. However, the mechanism is still unclear. This study aims to investigate the effects of T3 on the BAFF level and plasma cell ratio in bone marrow, spleen and peripheral blood of mice, and to explore the mechanism of T3 in affecting the mature and differentiation of B cells. Methods 80 C57BL/6J mice were randomly divided into control group and T3 group, and were given isotonic saline or T3 5/10μg once a day for 6 weeks, respectively. The levels of T3 in peripheral blood of each group were measured with ELISA. Flow cytometry was used to detect the proportion of B220+CD138+ plasma cells and IgM, IgG and IgD expression of B cells in the spleen, bone marrow and peripheral blood. Immunohistochemistry, Western blot and PCR were performed to determine the expression of BAFF in spleen and thyroid. ELISA was used to determine the expression of BAFF in peripheral blood. Results Compared with control group, the levels of T3 in peripheral blood, diet and drinking water in the T3 group were significantly increased after 6 weeks T3 intervention. The mRNA and protein expression of BAFF in spleen mononuclear cells of T3 group (2.03±0.52, 0.50±0.03) were higher than those in control group (1.06±0.19, 0.05±0.01) (P<0.01). HE staining showed that the white medulla in the spleen of the T3 group increased and merged. Flow cytometry indicated that the proportion of spleen plasma cells and antibody expression of B cells in T3 group [(3.92±1.55)%, (75.76±8.88)%] increased compared with control group [(2.43±1.18)%, (65.26±8.38)%] (P<0.05); Proportion of bone marrow plasma cells [(8.48±3.62)%] and antibody expression [(40.63±18.96)%] in T3 group were significantly increased compared with control group [(4.96±3.11)%, (22.89±7.32)%](P<0.05); Peripheral plasma cell ratio [(8.56±4.27)%] and antibody expression [(76.15±9.44)%] were lower than those in control group [(14.70±4.76)%, (84.20±3.98)%](P<0.05); Compared with control group [(5.98±0.78) pg/mL], the BAFF level in peripheral blood increased [(7.61±1.72) pg/mL] (P<0.01). Immunohistochemistry showed that the expression of BAFF increased in mononuclear cells of thyroid of the T3 group. Conclusion T3 could activate BAFF expression in bone marrow, spleen, peripheral blood and thyroid mononuclear cells, and induce differentiation of bone marrow and spleen B cells, thus causing pathological changes in thyroid tissue. Such mechanisms might play an important role in the pathogenesis of thyroid autoimmune diseases.