Deficiency of Immediate B Cell Precursors in Adult NZB

Animals wi th genet ical ly de te rmined defects in the deve lopment of l y m p h o i d and hemopoie t ic systems have proven useful for unde r s t and ing how these processes are normal ly regula ted (1-4). There is reason to believe that New Z e a l a nd strain mice, which have long been used as a model for a u t o i m m u n e disease, will s imilar ly be impor t an t for studies of B lymphocy te differentiat ion. These an imals are said to develop large numbers of polyc lonal ly ac t iva ted and secret ing cells together wi th B cells tha t are a typ ica l in terms of cell surface Ig and resistance to anti-/t ant ibodies , tolerance, and serum inhibi tors (5-10). M a n y of these features, which p r e suma b ly rela te to a u t o a n t i b o d y format ion, have been conferred on norma l i r r ad ia t ed recipients by graf t ing with New Zea l and Black mouse (NZB) hemopoie t ic cells (11-15). Such findings suggest tha t it might be possible to localize defects of their humora l i m m u n e system to the B l ineage or mic roenv i ronmenta l e lements that affect B cell format ion. It has recent ly become appa ren t tha t precursor cells capab le of giving rise to funct ional B cells d isp lay dis t inct ive surface ant igens and can ma tu re under appropr ia te cul ture condi t ions (16, 17). These and o ther character is t ics a l lowed us to compare such pre-B cell popula t ions in bone mar row of normal and NZB mice of different ages. D r a m a t i c t empora l changes were observed in the B cells and their precursors in NZB bone marrow, and this indicates tha t B cell format ion might v i r tua l ly cease in these an imals by adu l t life.