Diaw L, Siwarski D, Coleman A, Kim J, Jones G M, Dighiero G, Huppi K
Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Exp Med. 1999 Nov 15;190(10):1405-16. doi: 10.1084/jem.190.10.1405.
The many binding studies of monoclonal immunoglobulin (Ig) produced by plasmacytomas have found no universally common binding properties, but instead, groups of plasmacytomas with specific antigen-binding activities to haptens such as phosphorylcholine, dextrans, fructofuranans, or dinitrophenyl. Subsequently, it was found that plasmacytomas with similar binding chain specificities not only expressed the same idiotype, but rearranged the same light (V(L)) and heavy (V(H)) variable region genes to express a characteristic monoclonal antibody. In this study, we have examined by enzyme-linked immunosorbent assay five antibodies secreted by silicone-induced mouse plasmacytomas using a broader panel of antigens including actin, myosin, tubulin, single-stranded DNA, and double-stranded DNA. We have determined the Ig heavy and light chain V gene usage in these same plasmacytomas at the DNA and RNA level. Our studies reveal: (a) antibodies secreted by plasmacytomas bind to different antigens in a manner similar to that observed for natural autoantibodies; (b) the expressed Ig heavy genes are restricted in V gene usage to the V(H)-J558 family; and (c) secondary rearrangements occur at the light chain level with at least three plasmacytomas expressing both kappa and lambda light chain genes. These results suggest that plasmacytomas use a restricted population of B cells that may still be undergoing rearrangement, thereby bypassing the allelic exclusion normally associated with expression of antibody genes.
对浆细胞瘤产生的单克隆免疫球蛋白(Ig)进行的大量结合研究并未发现普遍共有的结合特性,相反,发现了几组对磷酰胆碱、葡聚糖、呋喃果聚糖或二硝基苯等半抗原具有特定抗原结合活性的浆细胞瘤。随后发现,具有相似结合链特异性的浆细胞瘤不仅表达相同的独特型,而且重排相同的轻链(V(L))和重链(V(H))可变区基因以表达特征性单克隆抗体。在本研究中,我们通过酶联免疫吸附测定法,使用包括肌动蛋白、肌球蛋白、微管蛋白、单链DNA和双链DNA在内的更广泛抗原组,检测了硅诱导的小鼠浆细胞瘤分泌的五种抗体。我们在DNA和RNA水平上确定了这些相同浆细胞瘤中Ig重链和轻链V基因的使用情况。我们的研究揭示:(a)浆细胞瘤分泌的抗体以与天然自身抗体类似的方式结合不同抗原;(b)所表达的Ig重链基因在V基因使用上局限于V(H)-J558家族;(c)轻链水平发生二次重排,至少有三个浆细胞瘤同时表达κ链和λ链基因。这些结果表明,浆细胞瘤利用了可能仍在进行重排的有限B细胞群体,从而绕过了通常与抗体基因表达相关的等位基因排斥。