Impaired rearrangement of IgH V to DJ segments in bone marrow Pro-B cells from old mice.

There are fewer bone marrow Pre-B cells in old compared to young mice. We have demonstrated both decreased rearrangement of the V to DJ IgH gene segments and low levels of VH germline transcripts in Pro-B cells, the precursors of Pre-B cells, from old compared to young mice. However, there was no difference in the level of RAG-mRNA in purified Pro-B cells from old and young mice. Consistent with the prior reports that fewer bone marrow emigrants enter the peripheral B cell populations of old than young mice, we identified fewer transitional B cells in the blood, as well as the spleen, of old than young mice. Association of impaired IgH rearrangement with a decreased number of transitional B cells in old mice was supported by finding that the percentage and number of transitional B cells expressing rearranged IgH and IgL transgenes, which do not require rearrangement of their endogenous IgH gene segments, were comparable in old and young mice. In contrast, the percentage and number of transitional B cells in these Ig-transgenic mice, which escaped allelic exclusion and have rearranged endogenous IgH gene segments, showed an age-associated decline similar to that seen in wild type mice. These data are consistent with the view that impaired V to DJ rearrangement contributes to the decreased levels of bone marrow Pre-B cells as well as the decreased levels of transitional B cells in the periphery.