Abstract
Current paradigms of peripheral B cell selection suggest that autoreactive B cells are controlled by clonal deletion, anergy, and developmental arrest. We report that changes to the human antibody repertoire likely resulting from these mechanisms both for a well-characterized autoreactivity from antibodies encoded by the VH4-34 gene and for other hallmarks of an autoreactive repertoire are apparent mainly for class-switched B cells and not for IgM germinal center, IgM memory, or IgM plasma cells. Other possible indicators of autoreactivity found selected with immunoglobulin class include JH6 gene segment usage, increased frequency of B cells with long third hypervariable regions, and distal Jκ gene segment bias. Of particular interest is the finding that B cells with these same characteristics are selected into the lineage of B cells that have undergone the unusual class switch from constant region Cμ to Cδ(Cδ-CS). The Cδ-CS population also displays an increased frequency of charged amino acids localized to the complementarity-determining regions, further suggesting autoreactivity, and evidence is presented that these B cells had undergone extensive receptor editing. Thus, the Cδ-CS lineage may be a "sink" for B cells harboring autoreactive specificities in normal humans. A model for a new tolerizing mechanism that could account for the Cδ-CS lineage is presented.
Recommended Citation
N. Y. Zheng and K. Wilson and X. Wang and A. Boston and G. Kolar and S. M. Jackson and Y. J. Liu and V. Pascual and J. D. Capra and P. C. Wilson, "Human Immunoglobulin Selection Associated With Class Switch And Possible Tolerogenic Origins For Cδ Class-switched B Cells," Journal of Clinical Investigation, vol. 113, no. 8, pp. 1188 - 1201, American Society for Clinical Investigation, Jan 2004.
The definitive version is available at https://doi.org/10.1172/JCI20255
Department(s)
Biological Sciences
Publication Status
Free Access
International Standard Serial Number (ISSN)
0021-9738
Document Type
Article - Journal
Document Version
Final Version
File Type
text
Language(s)
English
Rights
© 2025 The Authors, All rights reserved.
Creative Commons Licensing
This work is licensed under a Creative Commons Attribution 4.0 License.
Publication Date
01 Jan 2004
PubMed ID
15085198
Comments
National Center for Research Resources, Grant P20RR015577