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dc.contributor.authorNundel, Kerstin
dc.contributor.authorBusto, Patricia
dc.contributor.authorDebatis, Michelle E.
dc.contributor.authorMarshak-Rothstein, Ann
dc.date2022-08-11T08:08:29.000
dc.date.accessioned2022-08-23T15:57:11Z
dc.date.available2022-08-23T15:57:11Z
dc.date.issued2013-11-01
dc.date.submitted2014-05-13
dc.identifier.citation<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>
dc.identifier.issn0741-5400 (Linking)
dc.identifier.doi10.1189/jlb.0313126
dc.identifier.pmid23804807
dc.identifier.urihttp://hdl.handle.net/20.500.14038/30135
dc.description.abstractThe 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23804807&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttp://dx.doi.org/10.1189/jlb.0313126
dc.subjectAnimals
dc.subjectB-Lymphocytes
dc.subjectFemale
dc.subject*Lymphocyte Activation
dc.subjectMale
dc.subjectMice
dc.subjectMice, Inbred BALB C
dc.subjectMice, Inbred CBA
dc.subjectMice, Transgenic
dc.subjectProtein-Tyrosine Kinases
dc.subjectReceptors, Antigen, B-Cell
dc.subjectRheumatoid Factor
dc.subjectToll-Like Receptors
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectCell and Developmental Biology
dc.subjectCells
dc.subjectEnzymes and Coenzymes
dc.subjectImmunity
dc.titleThe role of Bruton's tyrosine kinase in the development and BCR/TLR-dependent activation of AM14 rheumatoid factor B cells
dc.typeJournal Article
dc.source.journaltitleJournal of leukocyte biology
dc.source.volume94
dc.source.issue5
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/374
dc.identifier.contextkey5574353
html.description.abstract<p>The 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.</p>
dc.identifier.submissionpathfaculty_pubs/374
dc.contributor.departmentDepartment of Medicine, Division of Rheumatology
dc.source.pages865-75


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