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Early arrest of B cell development in nude, X‐linked immune‐deficient mice

Mice simultaneously expressing the nude and xid mutations have a severe deficit of both mature T and B cells. We now report studies designed to determine at which point in B cell differentiation development is arrested. Nude‐xid mice have normal numbers of hematopoietic colony forming units (CFU‐s) but lack two early pre‐B cell markers: susceptibility to transformation by Abelson murine leukemia virus (A‐MuLV) and production of cytoplasmic μ (Cμ) heavy chain. Thus, there is a defect in lymphocyte development prior to or early in pre‐B cell differentiation but after hematopoietic stem cell formation. The monoclonal reagents DNL 1.9, 14.8 and RA3–3A1/6.1, which react with the surface protein B220 (Ly 5) on pro‐B, Cμ− pre‐B, Cμ+ pre‐B, and surface Ig+ B cells, revealed the presence of positive cells in nude‐xid mice. The bone marrow of nude‐xid mice contains more B220+ cells than Cμ+ cells. Our data suggest that the developmental block in these mice occurs at the earliest identifiable step in the B lymphocyte lineage, after the appearance of B220+ Cμ− pro‐ B cells, but before the differentiation of Cμ‐bearing (pre‐B) cells.