Essential Role of Apoptosis in Immature B Cells for Preventing Autoimmune Disease in Mice

Clonal deletion via programmed cell death is a key mechanism to eliminate these cells, as evidenced by autoimmune disease development in mice with defective B cell apoptosis. However, the specific stages of B cell development or activation where autoreactive B cells are deleted to prevent autoimmune diseases remain unclear.

Here, we directed anti-apoptotic Bcl-2 expression to early B cell progenitors in the bone marrow and to activated B cells.Our findings revealed that Bcl-2 expression during B cell development expanded peripheral transitional, anergic and follicular, but not bone marrow immature B cells. Follicular and anergic B cell accumulation were partly due to increased production.Notably, Bcl-2 expression during development, but not during activation, caused an antibody-dependent autoimmune disease with a specific autoantibody profile.