Elimination of self-reactive B lymphocytes proceeds in two stages: arrested development and cell death

SB Hartley, MP Cooke, DA Fulcher, AW Harris, S Cory… - Cell, 1993 - cell.com
SB Hartley, MP Cooke, DA Fulcher, AW Harris, S Cory, A Basten, CC Goodnow
Cell, 1993cell.com
In transgenic mice, self-reactive B lymphocytes are elimlnated if they encounter membrane-
bound self antlgene during their development within the bone marrow. We show here that
two separate and sequential events, arreated development and cell death, bring about B cell
elimination. Developmental arrest is an early outcome of antlgen binding in immature B
ceils, blocks acguisition of adhesion molecules and recep tors important for B cell migration
and activation, and is rapidly reversible by removal of antigen. Death of the arrested B cells …
Summary
In transgenic mice, self-reactive B lymphocytes are elimlnated if they encounter membrane-bound self antlgene during their development within the bone marrow. We show here that two separate and sequential events, arreated development and cell death, bring about B cell elimination. Developmental arrest is an early outcome of antlgen binding in immature B ceils, blocks acguisition of adhesion molecules and recep tors 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 detayed by expression of a M-2 tranegene, which results in e8cape of large number8 of self-reactive B cells from the bone marrow but fails to override the devefopmental arrest. These flndlngs define a novel pathway for Bcall ellmlnatlon, involving an initial stage vulnerable to breakdown in autoimmune disease.
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