Deletion and anergy of polyclonal B cells specific for ubiquitous membrane-bound self-antigen.
B cell tolerance to self-antigen is critical to preventing antibody-mediated autoimmunity. Previous work using B cell antigen receptor transgenic animals suggested that self-antigen-specific B cells are either deleted from the repertoire, enter a state of diminished function termed anergy, or are ignorant to the presence of self-antigen. These mechanisms have not been assessed in a normal polyclonal repertoire because of an inability to detect rare antigen-specific B cells. Using a novel detection and enrichment strategy to assess polyclonal self-antigen-specific B cells, we find no evidence of deletion or anergy of cells specific for antigen not bound to membrane, and tolerance to these types of antigens appears to be largely maintained by the absence of T cell help. In contrast, a combination of deleting cells expressing receptors with high affinity for antigen with anergy of the undeleted lower affinity cells maintains tolerance to ubiquitous membrane-bound self-antigens.
Department of Medicine and 2 Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Justin J
JJ
Taylor
Ryan J
RJ
Martinez
Philip J
PJ
Titcombe
Laura O
LO
Barsness
Stephanie R
SR
Thomas
Na
N
Zhang
Shoshana D
SD
Katzman
Marc K
MK
Jenkins
Daniel L
DL
Mueller
D019264:Adoptive Transfer; D000818:Animals; D001168:Arthritis / Q000276:immunology / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D017635:Clonal Anergy / Q000276:immunology*; D017637:Clonal Deletion / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D055503:Protein Multimerization; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism
D001324:Autoantigens; D017261:Glycosylphosphatidylinositols; D011947:Receptors, Antigen, B-Cell; D010047:Ovalbumin