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  • Until now there are no report

    2023-09-12

    Until now, there are no report regarding the relationship of CD21 and MG. In the present study, we aimed to characterize the AchR specified MK 571 and investigated the role of CD21 in immunopathogenesis of MG. We utilized the Allophycocyanin (APC)-conjugated AchR to measure the frequencies of AchR specified B cells in the periphery of MG patients, and further detected the CD21 expression on AchR specified B cells. We found that the levels of CD21+ AchR specified B cells correlated positively with serum anti-AchR IgG level, while the serum concentration of soluble CD21 correlated negatively with serum anti-AchR IgG level. Our data suggests that CD21 might facilitate its function on AchR specified B cell activation, resulting in the secretion of anti-AchR IgG.
    Materials and methods
    Results
    Discussion CD21, also called CR2, is located on B cell surface with three domains, an extracellular, transmembrane and cytoplasmic domain. Usually, CD21, coligated covalently with CD19 and CD81 on B cells, is responsible for sustenance of B cell survival as well as lowering threshold of B cell activation and reducing incidence of premature B cell apoptosis (Molnár et al., 2008, Erdei et al., 2009, Dunkelberger and Song, 2010). Aberrant CD21 expression is involved in dysregulation of immune responses. In murine models, CD21 deficiency reduced the incidence of autoimmune disease (Boackle et al., 2004, Del Nagro et al., 2005), impaired in activation of T cell responses and secondary autoantibody responses (Del Nagro et al., 2005), and lowered the serum IgG3 levels (Boackle et al., 2004). In human autoimmune disease, CD21 expression on B cells and sCD21 titers has been observed in body fluid of patients which showed inverse relationship with disease activity. The major findings of this study are the decreased level of membrane CD21 on B cells and serum sCD21 in the periphery of gMG patients, which are consistent with previous studies that serum membrane and secreted CD21 expression were decreased in patients of multiple sclerosis (Toepfner et al., 2012), juvenile arthritis (Singh et al., 2012), systemic lupus erythematosus (Masilamani et al., 2004a, Masilamani et al., 2004b), rheumatoid arthritis (Erdei et al., 2009) and antiphospholipid syndrome (Singh et al., 2008). As compared with other studies of the role of CD21 in autoimmune diseases, our study found levels of CD21+ B cells and serum sCD21 correlated negatively with anti-AchR IgG, which suggested that the levels of CD21+ B cells MK 571 and serum sCD21 might be indicative of anti-AchR IgG expression in an inverse relationship. The detailed relationship between CD21 decrease and anti-AchR IgG expression still needs exploration. For the first time, we investigated the frequencies of AchR specified B cells and CD21+ AchR specified B cells in peripheral blood of MG patients. Besides, other B cell populations involving IgG+ B cells, IgG+ AchR specified B cells were also detected in periphery of MG patients. In comparison with healthy controls, MG patients showed elevated frequencies of those B cell populations, suggesting CD21 along with AchR and IgG might participate in immunopathogenesis of MG. From correlation analysis, the frequencies of AchR specified B cells and CD21+ AchR specified B cells had positive correlations with anti-AchR IgG. Taken into account that CD21 is crucial for B cell survival and activation (Molnár et al., 2008), we defer that increased expression of CD21 on AchR specified B cells might contribute to the initiation and progression of MG by eliciting anti-AchR IgG production. The reason for CD21 decreases on B cells in MG needs to be explored. Previous studies suggested that membrane CD21 could be reduced in the following ways: (1) decreased transcription of CD21mRNA, (2) increased shedding of membrane CD21, (3) downregulation of CD21 mediated by ligands, such as C3b, IgE, and (4) increased terminal differentiation of CD21 (Boackle, 2005). In this study, we did not concern that the probability of CD21 decreased in the level of RNA transcription, because we did not detect any difference of mRNA level of CD21 between MG patients and healthy controls, even between the subgroup IIa and subgroup IIb. We excluded the possibility that the decrease of membrane CD21 on B cells was due to increased shedding of membrane CD21, for the reason that the levels of soluble sCD21 in serum and membrane CD21 on B cells were both decreased in periphery of MG patients. We were prone to consider that membrane CD21 was downregulated by ligation of ligands, for the level of membrane CD21 on B cells correlated negatively with the concentrations of anti-AchR IgG in the periphery of MG patients.