Molecular Characterization of Monoclonal IgM Derived from Human B Cell Lines Expressing the 4C9 Rheumatoid Factor Associated Idiotype

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Abstract
Ten human monoclonal B cell lines that express the RF associated Id 4C9 were analyzed using an immunogenetic approach. Five of eight tested lines were also strongly positive for the 6B6.6 Id. We found that all the 4C9/6B6.6 positive lines expressed VkIIIa light chain genes. In contrast, 4C9 reactivity was also found on a cell line expressing a VkIIIb light chain gene and on a line expressing a V light chain gene. The two anti-Ids recognized a linear light chain determinant on Humkv328 encoded light chains but also a conformational determinant on Vg encoded light chains that appeared to be dependent on the presence of a heavy chain. Idiotypic reactivity occurred on both RF positive and RF negative antibodies. Within this idiotypic system, the basis for idiotypic reactivity and RF reactivity is complex, subject to both heavy and light chain gene usage and sensitive to small numbers of somatic mutations.