Abstract
The murine acquired immunodeficiency syndrome (MAIDS) caused by defective LP-BM5 murine leukemia virus (MuLV) is a disease that shows severe immunodeficiency with abnormal lymphoproliferation, and hypergammaglobulinemia in susceptible C57BL/6 (B6) mice. To examine the cellular mechanisms of development of MAIDS, we injected LP-BM5 MuLV intraperitoneally into B6 mice bearing the X chromosome-linked immunodeficiency (xid). xid mice lack functionally mature B cells including Ly-1 B cells (also known as B-1 cells). All B6 mice died by 20 wk after LP-BM5 MuLV inoculation. In marked contrast, xid mice have continued to survive without any sign of MAIDS-related symptoms till at least 20 wk after the inoculation. The delayed progression of MAIDS in xid mice appears to depend on xid mutation, according to our experiments using both sexes of (B6.xid x B6)F1 and (B6 x B6.xid)F1 mice. Furthermore, Ly-1 B cells, enriched by a FACS, were shown to integrate the defective genome and appeared to be a major virus-infected B cell population. Our data corroborate that Ly-1 B cells play an important role in the induction and progression of MAIDS.
MeSH Terms
Animals
B-Lymphocytes/microbiology,pathology,physiology
Base Sequence
Blotting, Southern
Cell Division
DNA, Viral/genetics
Female
Genetic Linkage
Hypergammaglobulinemia/etiology
Immunity, Innate
Leukemia Virus, Murine/isolation & purification,physiology
Male
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Murine Acquired Immunodeficiency Syndrome/genetics,immunology,physiopathology
Mutation/genetics
Polymerase Chain Reaction
Retroviridae/isolation & purification,physiology
X Chromosome
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Hitoshi Y
Department of Immunology, University of Tokyo, Japan.
Okada Y
Sonoda E
Tominaga A
Makino M
Suzuki K
Kinoshita J
Komuro K
Mizuochi T
Takatsu K
References (30)
30 references, click to expand
-
X-linked B-lymphocyte immune defect in CBA/HN mice. I. Studies of the function and composition of spleen cells.
J Exp Med. 1975 Apr 1;141(4):788-803
PMID: 805203
-
Retrovirus-induced immunodeficiency in the mouse: MAIDS as a model for AIDS.
AIDS. 1992 Jul;6(7):607-21
PMID: 1503680
-
Peritoneal Ly-1 B cells: genetic control, autoantibody production, increased lambda light chain expression.
Eur J Immunol. 1986 Apr;16(4):450-6
PMID: 3084283
-
X-linked immune deficiency (xid) of CBA/N mice.
Curr Top Microbiol Immunol. 1986;124:87-101
PMID: 3486747
-
The Ly-1 B cell lineage.
Immunol Rev. 1986 Oct;93:81-102
PMID: 3096879
-
Evolution of B cell lineage lymphomas in mice with a retrovirus-induced immunodeficiency syndrome, MAIDS.
J Immunol. 1988 Feb 15;140(4):1123-31
PMID: 2830334
-
Normal, autoimmune, and malignant CD5+ B cells: the Ly-1 B lineage?
Annu Rev Immunol. 1988;6:197-218
PMID: 3289567
-
CD4+ T cells are required for development of a murine retrovirus-induced immunodeficiency syndrome (MAIDS).
J Exp Med. 1988 Aug 1;168(2):623-35
PMID: 2842430
-
Severe immunodeficiency disease induced by a defective murine leukaemia virus.
Nature. 1989 Apr 6;338(6215):505-8
PMID: 2538760
-
Defective virus is associated with induction of murine retrovirus-induced immunodeficiency syndrome.
Proc Natl Acad Sci U S A. 1989 May;86(10):3862-6
PMID: 2542949
-
Susceptibility to a mouse acquired immunodeficiency syndrome is influenced by the H-2.
Immunogenetics. 1989;30(4):266-72
PMID: 2551819
-
Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones.
J Exp Med. 1989 Dec 1;170(6):2081-95
PMID: 2531194
-
Immunodeficiency and clonal growth of target cells induced by helper-free defective retrovirus.
Science. 1989 Dec 22;246(4937):1614-7
PMID: 2480643
-
B cells are required for induction of T cell abnormalities in a murine retrovirus-induced immunodeficiency syndrome.
J Exp Med. 1990 Jan 1;171(1):315-20
PMID: 1967300
-
H-2-associated and background genes influence the development of a murine retrovirus-induced immunodeficiency syndrome.
J Immunol. 1990 Jun 1;144(11):4347-55
PMID: 2160500
-
Aberrant expression of cytokine genes in peritoneal macrophages from mice infected with LP-BM5 MuLV, a murine model of AIDS.
J Immunol. 1991 Jan 1;146(1):121-7
PMID: 1701789
-
Interleukin 10, a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells.
J Exp Med. 1990 Dec 1;172(6):1625-31
PMID: 2124252
-
Molecular cloning and expression of the murine interleukin-5 receptor.
EMBO J. 1990 Dec;9(13):4367-74
PMID: 2265612
-
Expression of defective virus and cytokine genes in murine AIDS.
J Virol. 1991 Feb;65(2):823-8
PMID: 1702843
-
A virus-encoded "superantigen" in a retrovirus-induced immunodeficiency syndrome of mice.
Science. 1991 Apr 19;252(5004):424-7
PMID: 1850169
-
The B-cell surface protein CD72/Lyb-2 is the ligand for CD5.
Nature. 1991 Jun 20;351(6328):662-5
PMID: 1711157
-
Characteristics and contributions of defective, ecotropic, and mink cell focus-inducing viruses involved in a retrovirus-induced immunodeficiency syndrome of mice.
J Virol. 1991 Aug;65(8):4232-41
PMID: 1649328
-
IL-10 inhibits cytokine production by activated macrophages.
J Immunol. 1991 Dec 1;147(11):3815-22
PMID: 1940369
-
The majority of cells infected with the defective murine AIDS virus belong to the B-cell lineage.
J Virol. 1991 Dec;65(12):6562-71
PMID: 1658361
-
CD4+ subset regulation in viral infection. Preferential activation of Th2 cells during progression of retrovirus-induced immunodeficiency in mice.
J Immunol. 1992 Jan 1;148(1):182-8
PMID: 1345785
-
The development and repertoire of B-1 cells (CD5 B cells).
Immunol Today. 1991 Nov;12(11):389-91
PMID: 1723875
-
Ly-1 B (B-1) cells are the main source of B cell-derived interleukin 10.
Eur J Immunol. 1992 Mar;22(3):711-7
PMID: 1547817
-
High frequency of transmission of murine AIDS virus in C57BL/10 mice via mother's milk.
J Virol. 1992 Sep;66(9):5177-82
PMID: 1323688
-
Presence of transplantable T-lymphoid cells in C57BL/6 mice infected with murine AIDS virus.
J Virol. 1992 Sep;66(9):5691-5
PMID: 1323720
-
CBA/N immune defective mice; evidence for the failure of a B cell subpopulation to be expressed.
Immunol Rev. 1982;64:117-36
PMID: 7044950