B cell repertoire in adult antigen-free and conventional neonatal BALB/c mice. I. Preferential utilization of the CH-proximal VH gene family PC7183.

Early in ontogeny B cells preferentially use VH gene families which are most adjacent to the genes coding for the constant part of the immunoglobulin molecule. In conventional adult mice, however, a random usage of VH gene families has been found. We investigated the role of exogenous antigenic stimulation on this normalization of VH gene usage by B cells. Therefore, we made use of adult germ-free BALB/c mice fed a chemically defined ultrafiltered antigen-free diet (GF-CD) and neonatal conventional BALB/c mice. Both the adult GF-CD and the newborn conventional mice represent situations with minimal exogenous antigenic stimulation. The results obtained with RNA dot blot hybridization with probes specific for the different VH gene families showed in hybridomas from adult GF-CD BALB/c mice a preferential usage of the CH-proximal VH gene family PC7183. In hybridomas from 5-day-old conventional BALB/c mice a less frequent usage of the J558 VH gene family was found and an increased usage of the PC7183 VH gene family than what would be expected from random usage. Evidence is presented that the RNA giving a positive signal with the PC7183 probe represents functional messages for IgM production.