1. Cross-Reactivity with Self-Antigen Tunes the Functional Potential of Naive B Cells Specific for Foreign Antigens.
- Author
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Steach HR, DeBuysscher BL, Schwartz A, Boonyaratanakornkit J, Baker ML, Tooley MR, Pease NA, and Taylor JJ
- Subjects
- Animals, Antibody Formation, Cell Differentiation, Cells, Cultured, Immunologic Memory, Lymphocyte Activation, Lymphocyte Count, Mice, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Antigen, B-Cell genetics, Autoantigens immunology, B-Lymphocyte Subsets immunology, B-Lymphocytes immunology, Cross Reactions immunology, Receptors, Antigen, B-Cell metabolism
- Abstract
Upon Ag exposure, naive B cells expressing BCR able to bind Ag can undergo robust proliferation and differentiation that can result in the production of Ab-secreting and memory B cells. The factors determining whether an individual naive B cell will proliferate following Ag encounter remains unclear. In this study, we found that polyclonal naive murine B cell populations specific for a variety of foreign Ags express high levels of the orphan nuclear receptor Nur77, which is known to be upregulated downstream of BCR signaling as a result of cross-reactivity with self-antigens in vivo. Similarly, a fraction of naive human B cells specific for clinically-relevant Ags derived from respiratory syncytial virus and HIV-1 also exhibited an IgM
LOW IgD+ phenotype, which is associated with self-antigen cross-reactivity. Functionally, naive B cells expressing moderate levels of Nur77 are most likely to proliferate in vivo following Ag injection. Together, our data indicate that BCR cross-reactivity with self-antigen is a common feature of populations of naive B cells specific for foreign Ags and a moderate level of cross-reactivity primes individual cells for optimal proliferative responses following Ag exposure., (Copyright © 2020 by The American Association of Immunologists, Inc.)- Published
- 2020
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