Guenzi S, Fra A M, Sparvoli A, Bet P, Rocco M, Sitia R
DIBIT-San Raffaele Scientific Institute, Milano, Italy.
Eur J Immunol. 1994 Oct;24(10):2477-82. doi: 10.1002/eji.1830241033.
Previous studies on IgM secretion demonstrated a role for the mu chain C-terminal cysteine (Cys575) in preventing the transport of unpolymerized subunits along the secretory pathway. The sequence homology between the C-terminal tailpieces of mu and alpha heavy chains prompted us to investigate the role of cysteine-mediated, retention in the control of IgA secretion during B cell development. Similar to IgM, IgA are not secreted by B lymphocytes: the retention mechanism can be reversed by the reducing agent 2-mercaptoethanol, suggesting that disulfide interchange reactions are involved in the quality control of both IgM and IgA. Yet, alpha 2L2 subunits, but not mu2L2, are secreted constitutively by plasma cells. We demonstrate that the differential retention of IgM and IgA subunits by myeloma transfectants is mainly due to the presence of an acidic residue upstream the alpha chain C-terminal cysteine. The regulation of polymeric Ig secretion during B cell development provides an example of how thiol-mediated quality control can be modulated according to the aminoacidic context surrounding the critical cysteine and to the cell type.
先前关于IgM分泌的研究表明，μ链C末端半胱氨酸（Cys575）在阻止未聚合亚基沿分泌途径转运中发挥作用。μ链和α重链C末端尾段之间的序列同源性促使我们研究半胱氨酸介导的滞留作用在B细胞发育过程中对IgA分泌的控制作用。与IgM相似，B淋巴细胞不分泌IgA：还原剂2-巯基乙醇可逆转这种滞留机制，这表明二硫键交换反应参与了IgM和IgA的质量控制。然而，α2L2亚基而非μ2L2亚基由浆细胞组成性分泌。我们证明，骨髓瘤转染子对IgM和IgA亚基的差异滞留主要是由于α链C末端半胱氨酸上游存在一个酸性残基。B细胞发育过程中聚合型Ig分泌的调控提供了一个例子，说明硫醇介导的质量控制如何根据关键半胱氨酸周围的氨基酸环境和细胞类型进行调节。
