title: B cell deficiency progresses with lineage maturation in nude.X-linked immunodeficient mice B cell deficiency progresses with lineage maturation.
abstract: Previously we showed that unlike normal, nude, or X-linked immune deficient (xid) mice, nude.xid mice are deficient in bone marrow pre-B cell targets for Abelson murine leukemia virus transformation. We show that nude.xid bone marrow is deficient in both CD45(B220)+ and CD45(B220)- surface (s)IgM- progenitors that give rise to B cell colonies in Whitlock-Witte cultures. CD45(B220)+ precursors had normal differentiation potential in vitro. CD45(B220)- precursors differentiated into CD45(B220)+ cells at the same rate as normal controls, but acquired sIgM at a much slower rate. These results correlated with the observation that in nude.xid mice the severity of B lineage defects correlates with maturity: a profound (ninefold) deficit of sIgM+, CD45(B220)+ mature B cells, a fivefold deficit in the sIgM-, CD45(B220)+ precursors of short term B cell colonies (colonies forming within 4-5 days in Whitlock-Witte cultures), and a moderate (twofold) decrease in the frequency of sIgM-, CD45(B220)- (less mature) precursors of long term B cell colonies (colonies forming after 14 days of Whitlock-Witte culture. Thus the combination of the nude and xid mutations produces a deficiency in early B cell progenitors and the deficiency becomes more profound with further maturation. Therefore the lack of mature B cells is the result of a cascade effect. Inasmuch as bone marrow progenitors are affected, and these are the source of the vast majority of B cells, most B cells are affected by the xid mutation and the xid defect cannot be attributed to a loss of a fetal lineage of B cells. These results suggest that xid affected cells lack the capacity to progress efficiently through differentiation in the absence of an exogenous factor(s) that is dependent on the product of a normal allele at the nude locus. This product might be supplied in vivo by a T cell or T cell-dependent source and/or epithelial elements such as bone marrow stromal cells all of which are known to be affected by the nude mutation.
authors.affiliation: Department of Pathology, Tufts University School of Medicine, Boston, MA 02111.
authors.forename: H Y
authors.initials: HY
authors.lastname: Chung
authors.forename: Z
authors.initials: Z
authors.lastname: Dong
authors.forename: H H
authors.initials: HH
authors.lastname: Wortis
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology*; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000473:pathology; D007075:Immunoglobulin M / Q000032:analysis; D007153:Immunologic Deficiency Syndromes / Q000276:immunology* / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D008819:Mice, Nude / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000032:analysis
chemical_list: D000954:Antigens, Surface; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D017493:Leukocyte Common Antigens