Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease.

TLDR

Transgenic mice expressing human BCL2 under an immunoglobulin heavy chain enhancer were used to study BCL2 functions. E mu‑bcl‑2‑22 mice exhibited excess B lymphocytes, prolonged B‑cell survival, amplified antibody responses, spontaneous anti‑nuclear antibodies, and 60 % developed immune‑complex glomerulonephritis, providing a model of systemic lupus erythematosus.

Abstract

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.