In vivo assessment of the relative contributions of deletion, anergy, and editing to B cell self-tolerance.
In normal B cell development, a large percentage of newly formed cells bear receptors with high levels of self-reactivity that must be tolerized before entry into the mature B cell pool. We followed the fate of self-reactive B cells expressing high affinity anti-hen egg lysozyme (HEL) Ag receptors exposed in vivo to membrane HEL in a setting in which the anti-HEL L chain was "knocked-in" at the endogenous L chain locus. These mice demonstrated extensive and efficient L chain receptor editing responses and had B cell numbers comparable to those found in animals lacking membrane Ag. BrdU labeling indicated that the time required for editing in response to membrane HEL was approximately 6 h. In mice transgenic for soluble HEL, anti-HEL B cells capable of editing showed evidence for both editing and anergy. These data identify receptor editing as a major physiologic mechanism by which highly self-reactive B cells are tolerized to membrane and soluble self-Ags.
Departments of Medicine and Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Keli.L.Hippen@tc.umn.edu
Keli L
KL
Hippen
Brian R
BR
Schram
Lina E
LE
Tze
Kathryn A
KA
Pape
Marc K
MK
Jenkins
Timothy W
TW
Behrens
D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D017635:Clonal Anergy / Q000235:genetics / Q000276:immunology*; D017637:Clonal Deletion / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018448:Models, Immunological; D009113:Muramidase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017393:RNA Editing / Q000235:genetics / Q000276:immunology*; D011828:Radiation Chimera / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism; D017634:Self Tolerance / Q000235:genetics / Q000276:immunology*; D012995:Solubility; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D000954:Antigens, Surface; D001324:Autoantigens; D011947:Receptors, Antigen, B-Cell; C421864:hen egg lysozyme; D009113:Muramidase