Unexpected autoantibody production in membrane Ig-mu-deficient/lpr mice

In the B lymphocyte lineage, Pas-mediated cell death is important in contro lling activated mature cells, but little is known about possible functions at earlier developmental stages. In this study we found that in mice lackin g the IgM transmembrane tail exons (mu MT mice), in which B cell developmen t is blocked at the pro-B stage, the absence of Fas or Pas ligand allows si gnificant B cell development and maturation, resulting in high serum Ig lev els. These B cells demonstrate Ig heavy chain isotype switching and autoimm une reactivity, suggesting that lack of functional Pas allows maturation of defective and/or self-reactive B cells in mu MT/lpr mice. Possible mechani sms that may allow maturation of these B cells are discussed.