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Publication : Cross-Reactivity with Self-Antigen Tunes the Functional Potential of Naive B Cells Specific for Foreign Antigens.

First Author  Steach HR Year  2020
Journal  J Immunol Volume  204
Issue  3 Pages  498-509
PubMed ID  31882518 Mgi Jnum  J:284023
Mgi Id  MGI:6388962 Doi  10.4049/jimmunol.1900799
Citation  Steach HR, et al. (2020) Cross-Reactivity with Self-Antigen Tunes the Functional Potential of Naive B Cells Specific for Foreign Antigens. J Immunol 204(3):498-509
abstractText  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.
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