Reconstitution of B cell function in murine models of immunodeficiency.
Murine models of immunodeficiency were used to evaluate strategies that might allow B cell engraftment in patients with X-linked agammaglobulinemia. Mice with defects in Btk or mu heavy chain were given 2.5 x 10(6) bone marrow cells from wild-type congenic donors. In the absence of any preparative regimen or immunosuppression, Btk-deficient mice on the CBA background developed normal concentrations of serum IgM and IgG3 by 12 weeks posttransplant. By contrast, mu heavy chain-deficient mice on the C57BL/6 background required some immunosuppression to achieve engraftment. Treatment of these mice with anti-T-cell antibodies 2 and 4 days prior to transplant resulted in normal concentrations of serum immunoglobulins by 6 weeks posttransplant. These pretreated mice had only 10% of the normal number of splenic B cells and they had no evidence of donor T cell engraftment. These results suggest that myelotoxic drugs may not be needed to achieve B cell engraftment in B-cell-deficient subjects.
Porpiglia
Andrea S
AS
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Rohrer
Jurg
J
Conley
Mary Ellen
ME
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004195:Disease Models, Animal; D005362:Ficoll / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007148:Immunoglobulin mu-Chains / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016513:Mice, SCID; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D005362:Ficoll; D004247:DNA; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase