• increased layers of synovial tissues in foot joints at 6 months of age

• arthritic lesions more pronounced at 14 months of age

• mild proliferative glomerulonephritis at 6 months age

• less than 50% of glomeruli affected

• by 14 months, 50% of mice with a lupus-like glomerulonephritis

• only about 80% of mice show long term MHC class II mismatch allograft survival (Bm12 into B6) compared to about 100% survival in wild-type mice

• however, survival time of MHC class I mismatch allografts is the same as wild-type controls

• mild proliferative glomerulonephritis at 6 months age

• less than 50% of glomeruli affected

• by 14 months, 50% of mice with a lupus-like glomerulonephritis

• increased layers of synovial tissues in foot joints at 6 months of age

• arthritic lesions more pronounced at 14 months of age

• start to die around 5 weeks of age, 2/3 are dead by 30 weeks

• massively enlarged hearts at death

• both ventricles dilated to about 2X normal diameter

• thin right venricular wall

• sporatic fibrosis and scar formation

• impaired pump function of the heart

• reduced movement of the ventricular walls and interventricular septum

• higher titers of autoantibodies (IgG1)

• deposition of IgG and C3 complement around cardiomyocytes

• varying degrees of hepatomegaly

• reduced movement of the ventricular walls and interventricular septum

• protrusion of eyeballs occurs a few weeks before death

• lymphoid cells in the peritoneal cavity increased about 2 fold

• increased numbers of B cells in the spleen

• B1 cells in the peritoneal cavity are increased

• proliferative response of B cells to anti-IgM is greatly enhanced

• myeloid lineages in the spleen are also increased

• moderate splenomegaly

• lymphoid cells in the peritoneal cavity increased about 2 fold

• increased numbers of B cells in the spleen

• B1 cells in the peritoneal cavity are increased

• proliferative response of B cells to anti-IgM is greatly enhanced

• myeloid lineages in the spleen are also increased

• moderate splenomegaly

• increased T cell independent antigen responses

• T cell dependent antigen responses were normal

• IgG2b levels were increased

• IgG3 levels were 3X normal

• proliferative response of B cells to anti-IgM is greatly enhanced

• increase in proliferation in response to fully MHC-mismatched stimulation

• increase is decreased by rapamycin treatment

• decreased survival time of cardiac allografts (source strain Bm12; 10.5 +/- 1.5 days) compared to mice homozygous for the Btla allele alone (14.3 +/- 3.8 days) or wild-type mice (over 100 days)

• increase in proliferation in response to fully MHC-mismatched stimulation

• increase is decreased by rapamycin treatment

• increase in proliferation in response to fully MHC-mismatched stimulation

• increase is decreased by rapamycin treatment

• in conjunction with anti-CTLA-4 antibody treatment, mice exhibit reduced paralysis induced by experimental autoimmune encephalomyelitis (EAE) compared to wild type mice

• however, adoptive transfer of Gt(ROSA)26Sor^tm2Awai Cd19^tm1(cre)Cgn double heterozygous B cells increases paralysis induced by EAE despite treatment with anti-CTLA-4 antibodies compared to wild-type mice receiving Gt(ROSA)26Sor^tm2Awai Cd19^tm1(cre)Cgn double heterozygous B cells