Age-related loss of bone marrow pre-B- and immature B-lymphocytes in the autoimmune-prone flaky skin mutant mice.

Defective B-lymphopoiesis has been associated with development of auto-antibodies and auto-immunity in a number of autoimmune-prone strains of mice. The flaky skin (fsn) mutation results in development of chronic inflammation and auto-immunity. Associated with the development of auto-immunity is the hyperactivation of B-lymphocytes and production of auto-antibodies. We, therefore, undertook a detailed examination of B-lineage precursors in the bone marrow of fsn/fsn mice. We observed a rapid age-related loss of the pre-B and immature B cells. It was also noted that an accumulation of early precursor populations occurs coincident with the loss of Fr.D and Fr.E bone marrow B cell populations indicating a developmental block or accumulation of pro-B cells in 7 and 10 week old fsn/fsn mice. Our data suggests changes in the fsn/fsn bone-marrow microenvironment that results in senescence of B cell development.