Role of antigen receptor affinity in T cell-independent antibody responses in vivo.
To examine how B cell receptor affinity affects clonal selection in thymus-independent type 2 (TI-2) immune responses, we produced mice with antibodies that showed a 40-fold difference in affinity for the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP). The difference in the responses of high- and low-affinity B cells to NP-Ficoll was only twofold. However, in competition experiments only the high-affinity B cells responded to antigen. CD19 deficiency increased the affinity threshold of TI-2 responses, whereas Lyn deficiency enhanced clonal expansion but abrogated B cell terminal differentiation. Thus, in TI-2 immune responses, large differences in affinity produce only small differences in the intrinsic ability of B cells to respond to antigen, and selection for high-affinity clones is due to clonal competition during the earliest stages of the response.
Shih
Tien-An Yang
TA
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021, USA.
Roederer
Mario
M
Nussenzweig
Michel C
MC
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology; D001667:Binding, Competitive; D015815:Cell Adhesion Molecules; D002455:Cell Division; D018390:Gene Targeting; D006241:Haptens / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D037102:Lectins; D051379:Mice; D008810:Mice, Inbred C57BL; D009596:Nitrophenols / Q000276:immunology*; D010648:Phenylacetates; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D051918:Sialic Acid Binding Ig-like Lectin 2; D013601:T-Lymphocytes / Q000276:immunology*; D019061:src-Family Kinases / Q000276:immunology
D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D006241:Haptens; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D037102:Lectins; D009596:Nitrophenols; D010648:Phenylacetates; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; C026242:4-hydroxy-5-nitrophenyl acetic acid; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases