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

Cell. 1993 Feb 12;72(3):325-35. doi: 10.1016/0092-8674(93)90111-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibody Formation
  • Autoimmunity*
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • Bone Marrow Cells
  • Cell Death
  • Mice
  • Mice, Transgenic
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-bcl-2


  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2