The role of Bruton's tyrosine kinase in the development and BCR/TLR-dependent activation of AM14 rheumatoid factor B cells
dc.contributor.author | Nundel, Kerstin | |
dc.contributor.author | Busto, Patricia | |
dc.contributor.author | Debatis, Michelle E. | |
dc.contributor.author | Marshak-Rothstein, Ann | |
dc.date | 2022-08-11T08:08:29.000 | |
dc.date.accessioned | 2022-08-23T15:57:11Z | |
dc.date.available | 2022-08-23T15:57:11Z | |
dc.date.issued | 2013-11-01 | |
dc.date.submitted | 2014-05-13 | |
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.issn | 0741-5400 (Linking) | |
dc.identifier.doi | 10.1189/jlb.0313126 | |
dc.identifier.pmid | 23804807 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/30135 | |
dc.description.abstract | 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. | |
dc.language.iso | en_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.url | http://dx.doi.org/10.1189/jlb.0313126 | |
dc.subject | Animals | |
dc.subject | B-Lymphocytes | |
dc.subject | Female | |
dc.subject | *Lymphocyte Activation | |
dc.subject | Male | |
dc.subject | Mice | |
dc.subject | Mice, Inbred BALB C | |
dc.subject | Mice, Inbred CBA | |
dc.subject | Mice, Transgenic | |
dc.subject | Protein-Tyrosine Kinases | |
dc.subject | Receptors, Antigen, B-Cell | |
dc.subject | Rheumatoid Factor | |
dc.subject | Toll-Like Receptors | |
dc.subject | Amino Acids, Peptides, and Proteins | |
dc.subject | Cell and Developmental Biology | |
dc.subject | Cells | |
dc.subject | Enzymes and Coenzymes | |
dc.subject | Immunity | |
dc.title | The role of Bruton's tyrosine kinase in the development and BCR/TLR-dependent activation of AM14 rheumatoid factor B cells | |
dc.type | Journal Article | |
dc.source.journaltitle | Journal of leukocyte biology | |
dc.source.volume | 94 | |
dc.source.issue | 5 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/faculty_pubs/374 | |
dc.identifier.contextkey | 5574353 | |
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.submissionpath | faculty_pubs/374 | |
dc.contributor.department | Department of Medicine, Division of Rheumatology | |
dc.source.pages | 865-75 |