Age-associated defects in B lymphocyte development.

The steady-state level of both RAG-1 and RAG-2 mRNA, the number of Pre-B cells, and the number of Pre-B cells expressing RAG-2 protein decrease in the bone marrow of old mice. These differences appear to be due, at least in part, to increased apoptosis of bone marrow Pre-B cells. To determine whether the age-associated increase in apoptosis reflects the impaired expression of the Pre-B cell receptor required for the survival of Pre-B cells, we examined the recombination of D to J and V to DJ in bone marrow from young and old mice. Both D to J recombination, which occurs early in the Pro-B cell stage of development, and V to DJ, which occurs just prior to the transition to the Pre-B cell stage, are diminished with age. These findings support the view that immunoglobulin recombination may impair the expression of the Pre-B cell receptor and may contribute to the increased rate of apoptosis of Pre-B cells in the bone marrow of old mice.