Activation and anergy in bone marrow B cells of a novel immunoglobulin transgenic mouse that is both hapten specific and autoreactive.
Available evidence indicates that B cell tolerance is attained by receptor editing, anergy, or clonal deletion. Here, we describe a p-azophenylarsonate (Ars)-specific immunoglobulin transgenic mouse in which B cells become anergic as a consequence of cross-reaction with autoantigen in the bone marrow. Developing bone marrow B cells show no evidence of receptor editing but transiently upregulate activation markers and appear to undergo accelerated development. Mature B cells are present in normal numbers but are refractory to BCR-mediated induction of calcium mobilization, tyrosine phosphorylation, and antibody responses. Activation marker expression and acquisition of the anergic phenotype is prevented in bone marrow cultures by monovalent hapten. In this model, it appears that induction of anergy in B cells can be prevented by monovalent hapten competing with autoantigen for the binding site.
Benschop
R J
RJ
Integrated Department of Immunology, National Jewish Medical and Research Center and, University of Colorado School of Medicine, Denver, CO 80206, USA.
Aviszus
K
K
Zhang
X
X
Manser
T
T
Cambier
J C
JC
Wysocki
L J
LJ
D000483:Alleles; D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000276:immunology*; D017635:Clonal Anergy / Q000276:immunology*; D004277:DNA, Single-Stranded / Q000276:immunology; D015870:Gene Expression; D006241:Haptens / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology; D007138:Immunoglobulin delta-Chains / Q000235:genetics / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000276:immunology; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000276:immunology; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D019076:Transgenes; D010132:p-Azobenzenearsonate / Q000276:immunology
D015415:Biomarkers; D004277:DNA, Single-Stranded; D006241:Haptens; D007138:Immunoglobulin delta-Chains; D007145:Immunoglobulin kappa-Chains; D007148:Immunoglobulin mu-Chains; D007136:Immunoglobulins; D010132:p-Azobenzenearsonate; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin