B cell receptor revision diminishes the autoreactive B cell response after antigen activation in mice
Ying-Hua Wang, Betty Diamond
Ying-Hua Wang, Betty Diamond
Published July 17, 2008
Citation Information: J Clin Invest. 2008;118(8):2896-2907. https://doi.org/10.1172/JCI35618.
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Research Article Immunology

B cell receptor revision diminishes the autoreactive B cell response after antigen activation in mice

Abstract

Autoreactive B cells are regulated in the BM during development through mechanisms, including editing of the B cell receptor (BCR), clonal deletion, and anergy. Peripheral B cell tolerance is also important for protection from autoimmune damage, although the mechanisms are less well defined. Here we demonstrated, using a mouse model of SLE-like serology, that during an autoimmune response, RAG was reinduced in antigen-activated early memory or preplasma B cells. Expression of RAG was specific to antigen-reactive B cells, required the function of the IL-7 receptor (IL-7R), and contributed to maintenance of humoral tolerance. We also showed that soluble antigen could diminish a non-autoreactive antibody response through induction of BCR revision. These data suggest that tolerance induction operates in B cells at a postactivation checkpoint and that BCR revision helps regulate autoreactivity generated during an ongoing immune response.

Authors

Ying-Hua Wang, Betty Diamond

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Figure 2

Characterization of antigen-reactive and nonreactive B cells.

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Characterization of antigen-reactive and nonreactive B cells. (A) qPCR a...
(A) qPCR analysis of transcripts of μ and γ1 chains in antigen-reactive and nonreactive B cells. (B) Sequence (Seq) analysis of VH and Vκ genes expressed by antigen-reactive B cells. Filled circles and triangles represent the number of point mutations in individual VH genes (n = 41) and Vκ genes (n = 26) expressed by Tet+B220lo cells. (C) qPCR analysis of Aid, Blimp1, and Xbp1 in antigen-reactive and nonreactive B cells. Data (mean ± SEM) are representative of 3 independent experiments (A and C). ND, not detected. Mice were immunized with DWEYS-MAP in CFA on day 0 and boosted with DWEYS-MAP in incomplete Freund adjuvant on day 7. Cells were sorted on day 16 (A–C). (D) Flow cytometry analysis of surface CD80 and CD95 on Tet+B220lo (solid line), Tet+B220hi (dotted line), and Tet–B220hi (line over shaded area) subsets. Mice were immunized with DWEYS-MAP in CFA on day 0 and boosted with DWEYS-MAP in incomplete Freund adjuvant on days 7 and 56. Spleen and BM cells were prepared 4 days after the second boost for analysis. Representative histogram from 4 to 5 mice was shown.