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

TLDR

Self‑reactive B cells are eliminated in transgenic mice when they encounter membrane‑bound self antigens during bone‑marrow development. The study demonstrates that B cell elimination occurs via two sequential stages: arrested development followed by cell death. The authors found that antigen binding induces an early, reversible developmental arrest that blocks adhesion and activation receptor acquisition, and that subsequent cell death within 1–3 days can be delayed by bcl‑2 expression, revealing a two‑stage elimination pathway susceptible to autoimmune disruption.

Abstract

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.