Hughey C T, Brewer J W, Colosia A D, Rosse W F, Corley R B
Department of Microbiology, Boston University School of Medicine, MA 02118-2526, USA.
J Immunol. 1998 Oct 15;161(8):4091-7.
Secreted IgM is predominantly found as pentameric molecules, but IgM can also be secreted as hexamers by B cell lines. Murine hexamers activate the complement cascade more efficiently than pentamers, but the physiologic significance of hexameric IgM remains unknown. Here, we report that IgM hexamers and pentamers are cleared from the circulation with similar kinetics, suggesting that the predominance of pentameric IgM in vivo reflects the regulation of polymer assembly and secretion in responding B cells. Normal IgM-secreting B cells, particularly those from the peritoneal cavity, are capable of secreting abundant hexameric IgM in vitro. The disparity between the ability of B cells to secrete IgM hexamers in vitro and the paucity of this polymer in vivo suggest that IgM hexamers might be deleterious. In support of this, we demonstrate that the autoantibodies from a number of patients with cold agglutinin (CA) disease include both IgM hexamers and pentamers. The CA IgM hexamers lyse human erythrocytes in the presence of human complement more efficiently than CA IgM pentamers, suggesting a potential role for hexameric IgM in the pathogenesis of this autoimmune syndrome.
分泌型IgM主要以五聚体分子形式存在，但IgM也可由B细胞系分泌为六聚体。小鼠六聚体比五聚体更有效地激活补体级联反应，但六聚体IgM的生理意义仍不清楚。在这里，我们报告IgM六聚体和五聚体以相似的动力学从循环中清除，这表明体内五聚体IgM的优势反映了反应性B细胞中聚合物组装和分泌的调节。正常分泌IgM的B细胞，特别是来自腹腔的B细胞，能够在体外分泌大量六聚体IgM。B细胞在体外分泌IgM六聚体的能力与体内这种聚合物的缺乏之间的差异表明IgM六聚体可能是有害的。为此，我们证明了一些冷凝集素（CA）病患者的自身抗体包括IgM六聚体和五聚体。CA IgM六聚体在人补体存在下比CA IgM五聚体更有效地裂解人红细胞，这表明六聚体IgM在这种自身免疫综合征的发病机制中具有潜在作用。
