Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease.
The biological functions of the BCL2 gene were investigated in transgenic mice harboring human BCL2 cDNA under the control of an immunoglobulin heavy chain enhancer (E mu). Mice of a representative transgenic strain, E mu-bcl-2-22, had a great excess of B lymphocytes, immunoglobulin-secreting cells, and serum immunoglobulins, attributable to increased longevity of B-lineage cells. Pre-B and plasma cells as well as B cells exhibited prolonged survival in culture. Immunized animals produced an amplified and protracted antibody response. Within the first year of life, most mice spontaneously produced antibodies to nuclear antigens, and 60% developed kidney disease, diagnosed as immune complex glomerulonephritis. Thus E mu-bcl-2-22 mice constitute a transgenic model for a systemic autoimmune disease resembling the human disorder systemic lupus erythematosus.
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
A
A
Strasser
S
S
Whittingham
D L
DL
Vaux
M L
ML
Bath
J M
JM
Adams
S
S
Cory
A W
AW
Harris
D000818:Animals; D000917:Antibody Formation; D000921:Antibody-Producing Cells / Q000166:cytology; D001327:Autoimmune Diseases / Q000235:genetics; D001402:B-Lymphocytes / Q000502:physiology*; D002470:Cell Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010950:Plasma Cells / Q000166:cytology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D013997:Time Factors
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2