B cell production and turnover in CBA/Ca, CBA/N and CBA/N-bcl-2 transgenic mice: xid-mediated failure among pre B cells is unaltered by bcl-2 overexpression.

The CBA/N strain carries xid, a murine btk missense mutation that reduces peripheral B cell numbers. Using in vivo BrdU labeling and cytofluorimetry, we have compared the magnitude, production rates, and turnover rates of each B lineage subset in the marrow and periphery of CBA/Ca and CBA/N mice. Our results show the pro-B compartment is largely unaffected by xid. In contrast, the pre-B cell pool is markedly reduced, reflecting a diminished production rate and unaltered turnover time. Despite diminished pre-B cell formation, the size of the immature B cell pool is relatively normal in CBA/N mice, due to increased proportional survival of pre-B cells. In addition, we have assessed the marrow and peripheral B cell subsets of CBA/N mice transgenic for bcl-2. These results indicate that while the bcl-2 transgene promotes lengthened survival in most B cell subsets, the pro/pre-B cell losses mediated by xid are not abrogated by bcl-2 overexpression. Taken together, these findings suggest that the initial [not readable: see text] from the pro- to pre-B cell pools, and that anomalies in subsequent compartments likely reflects the action of homeostatic mechanisms compensating for compromised pre-B cell production.