Spatz L A, Wong K K, Williams M, Desai R, Golier J, Berman J E, Alt F W, Latov N
Department of Neurology, College of Physicians and Surgeons of Columbia University, New York, NY 10032.
J Immunol. 1990 Apr 1;144(7):2821-8.
We have cloned and determined the nucleotide sequence of the Ig VH and VL region genes of an IgM kappa mAb that binds to denatured DNA and myelin from a patient (POP) with chronic lymphocytic leukemia and peripheral neuropathy. Sequence analysis indicates that the V region of the kappa L chain gene (PopVK) has 99% homology to a V kappa IIIa germ-line gene and the V region of the mu H chain gene (PopVH) has 96% homology to the VH26 germ-line gene that is a member of the VH3 gene family. It is likely the V kappa and VH genes arose from these respective germ-line genes via somatic mutation or from closely related genes. V kappa III genes have frequently been used by other IgMk mAb especially those with rheumatoid factor activity, and the VH26 gene with no somatic mutation has been used by several anti-DNA antibodies, suggesting the possibility of preferential association of these or related germ-line genes with autoantibodies. The minor differences between the sequences of POP's VH and V kappa genes and sequences used by other autoantibodies, may be responsible for this antibody's crossreactivity with myelin and, as a result, the autoimmune neuropathy.
我们克隆并测定了一种IgM κ单克隆抗体的Ig VH和VL区域基因的核苷酸序列，该抗体可与一名慢性淋巴细胞白血病和周围神经病变患者（POP）的变性DNA及髓磷脂结合。序列分析表明，κ轻链基因（PopVK）的V区域与VκIIIa种系基因有99%的同源性，μ重链基因（PopVH）的V区域与属于VH3基因家族的VH26种系基因有96%的同源性。Vκ和VH基因可能是通过体细胞突变从这些各自的种系基因产生，或者来自密切相关的基因。VκIII基因经常被其他IgMκ单克隆抗体使用，尤其是那些具有类风湿因子活性的抗体，而没有体细胞突变的VH26基因已被几种抗DNA抗体使用，这表明这些或相关种系基因与自身抗体优先关联的可能性。POP的VH和Vκ基因序列与其他自身抗体使用的序列之间的微小差异，可能是该抗体与髓磷脂发生交叉反应的原因，进而导致自身免疫性神经病变。
