Biomaterial Database

Efficient peripheral clonal elimination of B lymphocytes in MRL/lpr mice bearing autoantibody transgenes. 1998

J A Kench, and D M Russell, and D Nemazee

National Jewish Medical and Research Center, Division of Basic Sciences, Department of Pediatrics, Denver, Colorado 80206, USA.

Peripheral B cell tolerance was studied in mice of the autoimmune-prone, Fas-deficient MRL/ lpr.H-2(d) genetic background by introducing a transgene that directs expression of membrane-bound H-2Kb antigen to liver and kidney (MT-Kb) and a second transgene encoding antibody reactive with this antigen (3-83mu delta, anti-Kk,b). Control immunoglobulin transgenic (Ig-Tg) MRL/lpr.H-2(d) mice lacking the Kb antigen had large numbers of splenic and lymph node B cells bearing the transgene-encoded specificity, whereas B cells of the double transgenic (Dbl-Tg) MRL/lpr.H-2(d) mice were deleted as efficiently as in Dbl-Tg mice of a nonautoimmune B10.D2 genetic background. In spite of the severely restricted peripheral B cell repertoire of the Ig-Tg MRL/lpr.H-2(d) mice, and notwithstanding deletion of the autospecific B cell population in the Dbl-Tg MRL/lpr.H-2(d) mice, both types of mice developed lymphoproliferation and exhibited elevated levels of IgG anti-chromatin autoantibodies. Interestingly, Dbl-Tg MRL/lpr.H-2(d) mice had a shorter lifespan than Ig-Tg MRL/lpr.H-2(d) mice, apparently as an indirect result of their relative B cell lymphopenia. These data suggest that in MRL/lpr mice peripheral B cell tolerance is not globally defective, but that certain B cells with receptors specific for nuclear antigens are regulated differently than are cells reactive to membrane autoantigens.

UI	MeSH Term	Description	Entries
D006965	Hyperplasia	An increase in the number of cells in a tissue or organ without tumor formation. It differs from HYPERTROPHY, which is an increase in bulk without an increase in the number of cells.	Hyperplasias
D007106	Immune Sera	Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.	Antisera,Immune Serums,Sera, Immune,Serums, Immune
D008198	Lymph Nodes	They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.	Lymph Node,Node, Lymph,Nodes, Lymph
D008232	Lymphoproliferative Disorders	Disorders characterized by proliferation of lymphoid tissue, general or unspecified.	Duncan's Syndrome,X-Linked Lymphoproliferative Syndrome,Duncan Disease,Epstein-Barr Virus Infection, Familial Fatal,Epstein-Barr Virus-Induced Lymphoproliferative Disease In Males,Familial Fatal Epstein-Barr Infection,Immunodeficiency 5,Immunodeficiency, X-Linked Progressive Combined Variable,Lymphoproliferative Disease, X-Linked,Lymphoproliferative Syndrome, X-Linked, 1,Purtilo Syndrome,X-Linked Lymphoproliferative Disease,X-Linked Lymphoproliferative Disorder,Disease, Duncan,Disease, X-Linked Lymphoproliferative,Diseases, X-Linked Lymphoproliferative,Disorder, Lymphoproliferative,Disorder, X-Linked Lymphoproliferative,Disorders, Lymphoproliferative,Disorders, X-Linked Lymphoproliferative,Epstein Barr Virus Induced Lymphoproliferative Disease In Males,Epstein Barr Virus Infection, Familial Fatal,Familial Fatal Epstein Barr Infection,Immunodeficiency 5s,Immunodeficiency, X Linked Progressive Combined Variable,Lymphoproliferative Disease, X Linked,Lymphoproliferative Diseases, X-Linked,Lymphoproliferative Disorder,Lymphoproliferative Disorder, X-Linked,Lymphoproliferative Disorders, X-Linked,Lymphoproliferative Syndrome, X-Linked,Lymphoproliferative Syndromes, X-Linked,Purtilo Syndromes,Syndrome, Purtilo,Syndrome, X-Linked Lymphoproliferative,Syndromes, Purtilo,Syndromes, X-Linked Lymphoproliferative,X Linked Lymphoproliferative Disease,X Linked Lymphoproliferative Disorder,X Linked Lymphoproliferative Syndrome,X-Linked Lymphoproliferative Diseases,X-Linked Lymphoproliferative Disorders,X-Linked Lymphoproliferative Syndromes
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008822	Mice, Transgenic	Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.	Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D006183	H-2 Antigens	The major group of transplantation antigens in the mouse.	H2 Antigens,Antigens, H-2,Antigens, H2,H 2 Antigens
D000375	Aging	The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.	Senescence,Aging, Biological,Biological Aging
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001323	Autoantibodies	Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.	Autoantibody