| First Author | Nündel K | Year | 2019 |
| Journal | J Immunol | PubMed ID | 31534009 |
| Mgi Jnum | J:280800 | Mgi Id | MGI:6364683 |
| Doi | 10.4049/jimmunol.1900499 | Citation | Nundel K, et al. (2019) Cross-Reactive Antigen Expressed by B6 Splenocytes Drives Receptor Editing and Marginal Zone Differentiation of IgG2a-Reactive AM14 Vkappa8 B Cells. J Immunol 203(8):2055-2062 |
| abstractText | The AM14 BCR, derived from an autoimmune MRL/lpr mouse, binds autologous IgG2a(a/j) with low affinity, and as a result, AM14 B cells only proliferate in response to IgG2a immune complexes that incorporate DNA, RNA, or nucleic acid-binding proteins that serve as autoadjuvants. As such, AM14 B cells have served as a useful model for demonstrating the importance of BCR/TLR coengagement in the activation of autoreactive B cells. We now show that the same receptor recognizes an additional murine-encoded Ag, expressed by B6 splenocytes, with sufficient avidity to induce a TLR-independent proliferative response of BALB/c AM14 Vkappa8 B cells both in vivo and in vitro. Moreover, detection of this cross-reactive Ag by B6 AM14 Vkappa8 B cells promotes an anergic phenotype as reflected by suboptimal responses to BCR cross-linking and the absence of mature B cells in the bone marrow. The B6 Ag further impacts B cell development as shown by a dramatically expanded marginal zone compartment and extensive receptor editing in B6 AM14 Vkappa8 mice but not BALB/c AM14 Vkappa8 mice. Despite their anergic phenotypes, B6 AM14 Vkappa8 B cells can respond robustly to autoantigen/autoadjuvant immune complexes and could therefore participate in both autoimmune responses and host defense. |
