Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.
Department of Cardiology, Aerospace Center Hospital, Beijing, China.
Adv Exp Med Biol. 2024;1445:119-128. doi: 10.1007/978-981-97-0511-5_9.
Immunoglobulins (Igs) have been widely accepted to be exclusively expressed by B cells. Nonetheless, this theory is challenged by mounting evidence which suggests that Igs can also be generated by non B cells (non B-Ig), including cardiomyocytes (CM). Non B-Ig exhibits unique physical and chemical characteristics, unique variable region sequences and functions, which diverge from those of B-Ig. For instance, non B-Ig demonstrates hydrophobicity, limited diversity in the variable region, and extracellular matrix protein activity. Likewise, cardiomyocytes can express different classes of Igs, including IgM, IgG, and free Igκ light chains (cardiomyocyte derived-Igs, CM-Igs). In particular, CM-Igs can be secreted into the extracellular space in various cardiovascular diseases, such as myocardial ischaemia and myocardial fibrosis where they might be involved in complement activation and direct damage to cardiomyocytes. Nevertheless, the precise pathological activity of CM-Igs remains unclear. Recently, Zhu et al. focused on studying the sequence characteristics and functions of CM-Igκ; they discovered that the CM-Igκ exhibits a unique VJ recombination pattern, high hydrophobicity, and is principally located on the intercalated discs and cross striations of the cardiomyocytes. Interestingly, loss of Igκ in cardiomyocytes results in structural disorders in intercalated discs and dysfunction in myocardial contraction and conduction. Mechanically, Igκ promotes the stabilisation of plectin, a cytoskeleton cross-linker protein that connects desmin to desomsome, to maintain the normal structure of the intercalated disc. This finding indicates that CM-Igκ plays an integral role in maintaining cytoskeleton structure. Consequently, it is imperative to reveal the physiological functions and mechanisms of pathological injury associated with CM-Igs.
免疫球蛋白（Igs）被广泛认为仅由 B 细胞表达。然而，越来越多的证据表明，免疫球蛋白也可以由非 B 细胞（非 B-Ig）产生，包括心肌细胞（CM）。非 B-Ig 表现出独特的物理和化学特性、独特的可变区序列和功能，与 B-Ig 不同。例如，非 B-Ig 表现出疏水性、可变区多样性有限和细胞外基质蛋白活性。同样，心肌细胞可以表达不同类别的 Igs，包括 IgM、IgG 和游离 Igκ 轻链（心肌细胞衍生-Igs，CM-Igs）。特别是，CM-Igs 可以在各种心血管疾病（如心肌缺血和心肌纤维化）中分泌到细胞外空间，在这些疾病中，它们可能参与补体激活和直接损伤心肌细胞。然而，CM-Igs 的精确病理活性仍不清楚。最近，Zhu 等人专注于研究 CM-Igκ 的序列特征和功能；他们发现 CM-Igκ 表现出独特的 VJ 重组模式、高疏水性，主要位于心肌细胞的闰盘和交叉条纹上。有趣的是，心肌细胞中 Igκ 的缺失会导致闰盘结构紊乱和心肌收缩和传导功能障碍。从机制上讲，Igκ 促进细胞骨架交联蛋白 plectin 的稳定，plectin 将 desmin 连接到 desmosome，以维持闰盘的正常结构。这一发现表明 CM-Igκ 在维持细胞骨架结构中起着重要作用。因此，揭示与 CM-Igs 相关的生理功能和病理损伤机制至关重要。
