Bhat N M, Bieber M M, Chapman C J, Stevenson F K, Teng N N
Department of Gynecology and Obstetrics, Stanford Medical Center, CA 94305.
J Immunol. 1993 Nov 1;151(9):5011-21.
We describe two independently derived human mAb, A6(H4C5) and 216, initially selected for their reactivity to the lipid A domain of bacterial LPS, which also react with the following Ag: the i Ag present on cord RBC, a ligand on human B lymphocytes, and to certain autoantigens, defining these mAb as polyreactive. Both mAb have specific affinity for a carbohydrate epitope consisting minimally of a disaccharide with an acyl substitution at the 2-carbon position. Structural examination of the diverse Ag recognized by the two antibodies reveals the presence of this carbohydrate structure required for antibody binding. A6(H4C5) and 216 are IgM in isotype, but differ in their L chain expression. Molecular analysis shows that both the mAb are encoded by a highly conserved VH4 gene, designated VH4-21. This gene encodes a number of autoantibodies, particularly cold agglutinins. Specific recognition of lipid A and of a carbohydrate epitope on B lymphocytes by the two human mAb suggests a dual function for the highly conserved VH4-21 gene in antibacterial response and in B cell development and regulation.
我们描述了两种独立衍生的人源单克隆抗体，A6(H4C5)和216，最初因其对细菌脂多糖脂质A结构域的反应性而被选择，它们还与以下抗原发生反应：脐带红细胞上存在的i抗原、人B淋巴细胞上的一种配体以及某些自身抗原，这将这些单克隆抗体定义为多反应性。两种单克隆抗体对一种碳水化合物表位都具有特异性亲和力，该表位最少由一个在2-碳位置带有酰基取代的二糖组成。对这两种抗体识别的多种抗原进行结构检查发现，存在抗体结合所需的这种碳水化合物结构。A6(H4C5)和216的同种型为IgM，但它们的轻链表达有所不同。分子分析表明，这两种单克隆抗体均由一个高度保守的VH4基因编码，命名为VH4-21。该基因编码多种自身抗体，尤其是冷凝集素。这两种人源单克隆抗体对脂质A和B淋巴细胞上一种碳水化合物表位的特异性识别表明，高度保守的VH4-21基因在抗菌反应以及B细胞发育和调节中具有双重功能。
