B cell receptor expression level determines the fate of developing B lymphocytes: receptor editing versus selection.
During B lymphocyte development, antibody genes are assembled by DNA recombination. Successful cell surface expression of IgM promotes developmental progression. However, when antigen receptors bind autoantigen, development is blocked and ongoing antibody gene recombination occurs, which often alters antibody specificity in a process called receptor editing. We demonstrate here a significant role of developmental block and receptor editing in B cell receptor quality control. During development a functional, non-self-reactive receptor undergoes receptor editing if its expression is below a certain threshold. Doubling the receptor gene dose promotes development in the absence of autoantigen, but allows editing when autoantigen is present. Thus, both underexpressed and harmful B cell receptors can undergo correction by receptor editing.
Kouskoff
V
V
Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Lacaud
G
G
Pape
K
K
Retter
M
M
Nemazee
D
D
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology*; D011995:Recombination, Genetic / Q000276:immunology
D011947:Receptors, Antigen, B-Cell