Identification of anergic B cells within a wild-type repertoire.
The contribution of anergy to silencing of autoreactive B cells in physiologic settings is unknown. By comparing anergic and nonanergic immunoglobulin-transgenic mouse strains, we defined a set of surface markers that were used for presumptive identification of an anergic B cell cohort within a normal repertoire. Like anergic transgenic B cells, these physiologic anergic cells exhibited high basal intracellular free calcium and did not mobilize calcium, initiate tyrosine phosphorylation, proliferate, upregulate activation markers, or mount an immune response upon antigen-receptor stimulation. Autoreactive B cells were overrepresented in this cohort. On the basis of the frequency and lifespan of these cells, it appears that as many as 50% of newly produced B cells are destined to become anergic. In conclusion, our findings indicate that anergy is probably the primary mechanism by which autoreactive B cells are silenced. Thus maintenance of the unresponsiveness of anergic cells is critical for prevention of autoimmunity.
Merrell
Kevin T
KT
Integrated Department of Immunology, University of Colorado Health Sciences Center and National Jewish Medical Research Center, Denver, Colorado 80206, USA.
Benschop
Robert J
RJ
Gauld
Stephen B
SB
Aviszus
Katja
K
Decote-Ricardo
Debora
D
Wysocki
Lawrence J
LJ
Cambier
John C
JC
D000818:Animals; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D017635:Clonal Anergy / Q000276:immunology*; D005434:Flow Cytometry; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D011951:Receptors, Complement / Q000276:immunology / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism; D017634:Self Tolerance / Q000276:immunology*
D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D011951:Receptors, Complement; D017455:Receptors, IgE; C032402:complement 1q receptor