nemazee had been studying the deletion of autoreactive b cells in transgenic mice whose b cells all expressed receptors specific for a particular mhc molecule . when this transgene was bred onto mice that expressed that mhc protein ,
as expected , these mice lacked autoreactive b cells in the periphery . but to nemazee 's surprise , a large pool of autoreactive b cells persisted in the bone marrow ( 3 ) .
to pinpoint the exact step at which the cells were escaping deletion , nemazee and his team engineered strains in which the autoantigen was targeted to different anatomical locations .
expression of autoantigen in just the liver caused a near complete deletion of anti - mhc b cells , which were not replaced by non - autoreactive counterparts .
but when autoantigen was also present in the bone marrow , there were many more peripheral b cells that were no longer self - reactive .
nemazee discovered that these cells had escaped by switching antibody receptors  they had new light chains derived from a rearranged version of the endogenous gene .
the alterations took place in immature b cells , as nemazee only detected the rearrangements in bone marrow b cells .
light chain replacement was simultaneously demonstrated in a different transgenic model by martin weigert and his team at the fox chase cancer center ( philadelphia , pa ) . while studying lupus , weigert had designed mice that carried a transgene for an anti - dna antibody .
younger mice had fewer b cells , suggesting that autoreactive clones had been deleted . but adult mice had normal numbers of b cells .
weigert and nemazee published their seminal results in a series of papers in the journal of experimental medicine in 1993 ( 46 ) .
the studies were at first controversial , but numerous reports from other groups have since bolstered the case for receptor editing as a major mechanism for tolerance ( 7 ) .
it is now estimated that at least 25% of b cells in the repertoire have undergone receptor editing ( 8) .
nemazee 's anti - mhc transgenic mouse model has since been modified such that transgenes insert specifically into the heavy and light chain loci ( 9 ) .
repairing its receptors rather than throwing away the whole cell might be the most efficient way to generate a diverse , non - self - reactive repertoire .
 in 1993 , david nemazee and martin weigert independently showed that autoreactive b cells could proofread , alter , and reexpress modified receptors to become nonautoreactive . 
 this process , called  receptor editing ,  has since gained prominence as the main mechanism of b cell tolerance . 
Death-defying B cells
B cells repair their receptors
Improving on dogma