Different sensitivity to receptor editing of B cells from mice hemizygous or homozygous for targeted Ig transgenes

Ig knock-in mice have been used to study the relative contribution of recep tor selection versus clonal selection in the control of autoreactive B cell s. The anti-MHC class I 3-83Ig knock-in (3-83Igi) mice manifest extensive r eceptor editing in the presence of H-2(b). However, receptor editing is als o observed on the H-2(d) background, although reactivity toward this antige n is below detection and its presence does not affect the generation of 3-8 3Ig(+) mature B cells in classical 3-83Ig transgenic mice. In this study we have analyzed the contribution of genetic background. B cell receptor sign aling, and transgene copy number on the initiation and extent of receptor e diting in the 3-83Igi;H-2(d) mice. Crossing the 3-83Ig insertion into eithe r CD45-deficient H-2(d) mice or onto the BALB/c background reduces the exte nt of receptor editing and increases the fraction of 3-83Ig-expressing B ce lls, indicating that in the original line editing depends on B cell recepto r signaling induced by cross-reacting antigen(s). However, receptor editing is still detectable in hemizygous 3-83Igi mice even on the BALB/c backgrou nd, on which the 3-83 antibody was originally raised, whereas it is abrogat ed in homozygous 3-83Igi;H-2(d) animals. This latter observation indicates that immature B cells expressing immunoglobulin from single heavy and light chain loci, as they do physiologically, utilize receptor editing for an ex quisite quality control of their antigen receptor that may only partly be b ased on self-reactivity.