High connectivity, natural antibodies preferentially use 7183 and QUPC 52 VH families.

Twenty-seven B cell hybridomas derived from spleen cells of nonimmunized, 6-day-old BALB/c mice and previously characterized serologically were screened for VH-gene expression: hybridomas expressing the two most D-proximal VH-gene families, 7183 and QUPC 52 were over-represented in this sample. Strikingly, clones serologically characterized by high degree of degenerate "specificity" and high idiotypic connectivity were found to use almost exclusively these two VH-gene families. As these serological properties are a unique feature of "natural" antibody repertoires, the results may reflect a functional relationship between expression of these VH genes and activation of B cells in the internal environment, particularly in the context of idiotypic interactions.