Role of antigen receptor affinity in T cell–independent antibody responses in vivo

TAY Shih, M Roederer, MC Nussenzweig - Nature immunology, 2002 - nature.com
Nature immunology, 2002nature.com
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 …
Abstract
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.
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