Nundel, KerstinBusto, PatriciaDebatis, Michelle E.Marshak-Rothstein, Ann2022-08-232022-08-232013-11-012014-05-13<p>Nundel K, Busto P, Debatis M, Marshak-Rothstein A. The role of Bruton's tyrosine kinase in the development and BCR/TLR-dependent activation of AM14 rheumatoid factor B cells. J Leukoc Biol. 2013 Nov;94(5):865-75. doi: 10.1189/jlb.0313126. <a href="http://dx.doi.org/10.1189/jlb.0313126">Link to article on publisher's site</a></p>0741-5400 (Linking)10.1189/jlb.031312623804807https://hdl.handle.net/20.500.14038/30135The protein kinase Btk has been implicated in the development, differentiation, and activation of B cells through its role in the BCR and TLR signaling cascades. These receptors and in particular, the BCR and either TLR7 or TLR9 also play a critical role in the activation of autoreactive B cells by RNA- or DNA-associated autoantigens. To explore the role of Btk in the development of autoreactive B cells, as well as their responses to nucleic acid-associated autoantigens, we have now compared Btk-sufficient and Btk-deficient mice that express a prototypic RF BCR encoded by H- and L-chain sdTgs. These B cells bind autologous IgG2a with low affinity and only proliferate in response to IgG2a ICs that incorporate DNA or RNA. We found that Btk-sufficient RF(+) B cells mature into naive FO B cells, all of which express the Tg BCR, despite circulating levels of IgG2a. By contrast, a significant proportion of Btk-deficient RF(+) B cells acquires a MZ or MZ precursor phenotype. Remarkably, despite the complete inability of RF(+) Xid/y B cells to respond to F(ab')2 anti-IgM, RF(+) Xid/y B cells could respond well to autoantigen-associated ICs. These data reveal unique features of the signaling cascades responsible for the activation of autoreactive B cells.en-USAnimalsB-LymphocytesFemale*Lymphocyte ActivationMaleMiceMice, Inbred BALB CMice, Inbred CBAMice, TransgenicProtein-Tyrosine KinasesReceptors, Antigen, B-CellRheumatoid FactorToll-Like ReceptorsAmino Acids, Peptides, and ProteinsCell and Developmental BiologyCellsEnzymes and CoenzymesImmunityJournal Articlehttps://escholarship.umassmed.edu/faculty_pubs/3745574353faculty_pubs/374