Immunodeficiency of alymphoplasia mice (aly/aly) in vivo: structural defect of secondary lymphoid organs and functional B cell defect.
Alymphoplasia mice (aly/aly) have been shown to be deficient for a nuclear factor-kappaB-inducing kinase involved in signal transduction of lymphotoxin beta receptor (LT-betaR) and of CD40, resulting in structural defects of secondary lymphoid organs and highly increased susceptibility to viral infections. We analyzed the anti-viral immune response of bone marrow chimeras (BMC) between aly/aly mice and (C57BL/6 x DBA2)F1 mice (B6D2F1) to evaluate in vivo whether the structural defects of secondary lymphoid organs or intrinsic B or T cell defects led to immunodeficiency in aly/aly mice. Transfer of aly/aly bone marrow into B6D2F1 mice (aly/aly-->B6D2F1) led to excellent T but poor B cell reconstitution of recipients. Antiviral cytotoxic T cell (CTL) responses of aly/aly-->B6D2F1 BMC were clearly improved compared to aly/aly mice whereas virus-neutralizing IgG reponses were virtually absent. Therefore, the inefficient CTL response was predominantly caused by the structural defect of secondary lymphoid organs and not by an intrinsic T cell defect. In contrast, B cells of aly/aly origin were unable to undergo isotype switch after viral infections, indicating an intrinsic B cell defect in vivo. Overall, aly/aly mice show the combined immunodeficient phenotype of mice deficient for LT-3R with B cells functionally deficient for CD40.
Karrer
U
U
Institute of Experimental Immunology, Department of Pathology, University Hospital of Zurich, Zürich, Switzerland. urs.karrer@ndm.ox.ac.uk
Althage
A
A
Odermatt
B
B
Hengartner
H
H
Zinkernagel
R M
RM
D000361:Agammaglobulinemia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000473:pathology*; D016026:Bone Marrow Transplantation; D019013:CD40 Antigens / Q000032:analysis; D003602:Cytotoxicity, Immunologic; D018792:Encephalitis, Viral / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008099:Liver / Q000821:virology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology / Q000302:isolation & purification; D008221:Lymphoid Tissue / Q000002:abnormalities* / Q000821:virology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D011828:Radiation Chimera; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000821:virology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology / Q000472:pathogenicity; D019562:Viral Load; D014766:Viremia / Q000821:virology
D000914:Antibodies, Viral; D019013:CD40 Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M