Elimination of self-reactive B lymphocytes proceeds in two stages: arrested development and cell death.
In transgenic mice, self-reactive B lymphocytes are eliminated if they encounter membrane-bound self antigens during their development within the bone marrow. We show here that two separate and sequential events, arrested development and cell death, bring about B cell elimination. Developmental arrest is an early outcome of antigen binding in immature B cells, blocks acquisition of adhesion molecules and receptors important for B cell migration and activation, and is rapidly reversible by removal of antigen. Death of the arrested B cells occurs within 1 to 3 days and can be delayed by expression of a bcl-2 transgene, which results in escape of large numbers of self-reactive B cells from the bone marrow but fails to override the developmental arrest. These findings define a novel pathway for B cell elimination, involving an initial stage vulnerable to breakdown in autoimmune disease.
Hartley
S B
SB
Howard Hughes Medical Institute, Stanford University School of Medicine, California 94305.
Cooke
M P
MP
Fulcher
D A
DA
Harris
A W
AW
Cory
S
S
Basten
A
A
Goodnow
C C
CC
D000818:Animals; D000917:Antibody Formation; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D001854:Bone Marrow Cells; D016923:Cell Death; D051379:Mice; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2