众所周知,免疫球蛋白(Ig)仅由B谱系细胞产生。Ig基因是通过一组基因片段的重排而产生的[变量(V),多样性(D),和连接(J)段重排,或V(D)J重组],这导致负责识别各种抗原的B细胞衍生的Ig的巨大多样性。Ig随后在暴露于抗原后经历体细胞超突变(SHM)和类别转换重组(CSR)。从而将低亲和力IgM转化为IgG,IgA,或IgE抗体。IgM和IgD主要在未暴露于抗原的原始B细胞中表达,它们不会发生体细胞超突变;因此,它们的可变区序列保持与种系中的那些相同。相比之下,IgG,IgA,IgE在抗原刺激的记忆B细胞或浆细胞中表达,因此,它们通常在其可变区序列中具有高频突变。自从发现Ig可以由非B细胞产生以来,邱氏小组对B细胞源性Ig和非B细胞源性Ig的遗传特征进行了调查和比较。这些发现表明,非B细胞来源的Ig与B细胞来源的Ig具有某些相似性,因为其恒定区的序列与B细胞来源的Ig相同。它的可变区也严格依赖于V的重排,D,和J基因片段。此外,类似于B细胞衍生的Ig,IgM和IgD的V区很少发生突变,而IgG,IgA,癌细胞产生的IgE经常发生突变。然而,非B细胞衍生的IgV区序列表现出独特的特征。(1)与B细胞来源的Ig的巨大多样性不同,非B细胞来源的Ig表现出有限的多样性;来自相同谱系的细胞总是选择相同的V(D)J重组模式;(2)在Ig阳性癌细胞系和正常组织中检测到RAG1/RAG2重组酶的mRNA和蛋白。但是在RAG1-/-和RAG2-/-小鼠中也可以发现Ig重组,这表明它们对于非B细胞衍生的Ig的重排不是必需的。非B细胞衍生的Ig的这些特征表明V(D)J重组的潜在未被发现的机制,结扎,和SHM在非B细胞中,这就需要用先进的分子生物学技术进行进一步的研究。
It is widely acknowledged that immunoglobulins (Igs) are produced solely by B-lineage cells. The Ig gene is created by the rearrangement of a group of gene segments [variable (V), diversity (D), and joining (J) segments rearrangement, or V(D)J recombination], which results in the vast diversity of B cell-derived Ig responsible for recognising various antigens. Ig subsequently undergoes somatic hypermutation (SHM) and class switch recombination (CSR) after exposure to antigens, thus converting the low-affinity IgM to IgG, IgA, or IgE antibodies. IgM and IgD are primarily expressed in naïve B cells that have not been exposed to antigens, they do not undergo somatic hypermutation; hence, their variable region sequences remain the same as those in the germline. In contrast, IgG, IgA, and IgE are expressed in antigen-stimulated memory B cells or plasma cells, and thus, they often possess high-frequency mutations in their variable region sequences. Since the discovery that Ig can be produced by non-B cells, Qiu\'s group has investigated and compared the genetic characteristics of B cell-derived Ig and non-B cell-derived Ig. These findings demonstrated that non-B cell-derived Ig shares certain similarities with B cell-derived Ig in that the sequence of its constant region is identical to that of B cell-derived Ig, and its variable region is also strictly dependent on the rearrangement of V, D, and J gene segments. Moreover, akin to B cell-derived Ig, the V regions of IgM and IgD are rarely mutated, while IgG, IgA, and IgE produced by cancer cells are frequently mutated. However, the non-B cell-derived Ig V region sequence displays unique characteristics. (1) Unlike the vast diversity of B cell-derived Igs, non-B cell-derived Igs exhibit restricted diversity; cells from the same lineage always select the same V(D)J recombination patterns; (2) Both mRNA and proteins of RAG1/RAG2 recombinase have been detected in Ig positive cancer cell lines and normal tissues. But Ig recombination could also be found in RAG1-/- and RAG2-/- mice, suggesting that they are not necessary for the rearrangement of non-B cell-derived Igs. These features of non-B cell-derived Igs suggest a potentially undiscovered mechanism of V(D)J recombination, ligation, and SHM in non-B cells, which necessitates further investigation with advanced technology in molecular biology.