Biased expression of variable region gene families of the immunoglobulin heavy chain in autoimmune-prone mice

We have examined usage of variable region gene families of the immunoglobulin heavy chain (VH gene family) in spleens of MRL/MpJ-1pr/lpr (MRL/lpr), (NZB x NZW)F1, and BXSB mice by Northern analysis using various VH probes, including the VHPAR gene which we cloned and identified as a gene encoding the heavy-chain variable region of antipoly(ADP-ribose) antibody. The amount of VHS107 family mRNA was almost constant for the same amount of splenic crude RNA in autoimmune-prone and normal mice, while concentrations of other family mRNAs were elevated in autoimmune-prone mice. For example, per splenic RNA the VHPAR family was expressed in MRL/lpr mice 10 times more than in their normal counterpart, MRL/MpJ-+/+ (MRL/+) mice. These results indicate the bias of VH gene usage in autoimmune-prone mice. Expression of the VHS107 family was depressed from an early life stage of MRL/lpr and male BXSB mice. Furthermore, the expression of IL-4 and IL-5 were quantitatively compared, as B cell differentiation factor was thought to be produced by abnormally proliferative T cells in lymph nodes of MRL/lpr mice. We could not, however, observe overproduction of IL-4 and IL-5 mRNA in the lymph nodes.