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 receptor selection versus clonal selection in the control of autoreactive B cells. The anti-MHC class I 3-83Ig knock-in (3-83Igi) mice manifest extensive receptor editing in the presence of H-2(b). However, receptor editing is also observed on the H-2(d) background, although reactivity toward this antigen is below detection and its presence does not affect the generation of 3-83Ig(+) mature B cells in classical 3-83Ig transgenic mice. In this study we have analyzed the contribution of genetic background, B cell receptor signaling, and transgene copy number on the initiation and extent of receptor editing in the 3-83Igi;H-2(d) mice. Crossing the 3-83Ig insertion into either CD45-deficient H-2(d) mice or onto the BALB/c background reduces the extent of receptor editing and increases the fraction of 3-83Ig-expressing B cells, indicating that in the original line editing depends on B cell receptor signaling induced by cross-reacting antigen(s). However, receptor editing is still detectable in hemizygous 3-83Igi mice even on the BALB/c background, on which the 3-83 antibody was originally raised, whereas it is abrogated 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 exquisite quality control of their antigen receptor that may only partly be based on self-reactivity.
Braun
U
U
Max Planck Institute for Immunobiology, Stübeweg 51 D-79108 Freiburg, Germany.
Rajewsky
K
K
Pelanda
R
R
D000818:Animals; D018390:Gene Targeting; D005803:Genes, Immunoglobulin; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology*; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000235:genetics* / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D011947:Receptors, Antigen, B-Cell