Age-dependent deficiency of B lymphocyte lineage precursors in NZB mice

Adult NZB mice (greater than 15 wk old) have very few bone marrow cells that can give rise to sIg+ clonable B cells during liquid culture. This deficiency corresponds to extremely low numbers of cells with cytoplasmic but not surface mu chains of IgM and reduced numbers of cells bearing a high molecular weight B-lineage antigen. Depletion of Thy-1-bearing cells and appropriate mixing experiments did not provide evidence either that suppressor cells are responsible for this phenomenon or that accessory cells are defective in NZB mice. Nor did it seem that B cells were being produced in extramedullary sites. B cell precursors were detectable in very young NZB mice, exceeded control values at 4-5 wk of age, and then declined rapidly. In contrast, these persisted for greater than 1 yr in normal BALB/c, DBA/2, and CBA/H mice. It appears possible that intermediate stages in B-lineage differentiation become prematurely exhausted through an accelerated aging process in NZB mice. These chronological changes have implications for understanding the sequence of events that lead to B lymphocyte formation and the processes that normally regulate it.