Using a panel of antibodies specific for H and L chain variable region subgroups, a panel of human monoclonal cold agglutinin (CA) and rheumatoid factor (RF) autoantibodies were analyzed. The vast majority of the two types of autoantibodies utilized VkIII L chains, many of which probably derive from the Humkv325 gene. However, while most RFs (77%) utilized VHI H chains, all the CAs used VHII subgroup H chains. These results are consistent with a model of autoantibody generation, wherein binding specificity is H chain defined in a set of antibodies that use a multipotential L chain.

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