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Loss of anergic B cells in prediabetic and new-onset type 1 diabetic patients.
Smith, Mia J; Packard, Thomas A; O'Neill, Shannon K; Henry Dunand, Carole J; Huang, Min; Fitzgerald-Miller, Lisa; Stowell, Daniel; Hinman, Rochelle M; Wilson, Patrick C; Gottlieb, Peter A; Cambier, John C.
Afiliação
  • Smith MJ; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO.
  • Packard TA; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO.
  • O'Neill SK; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO.
  • Henry Dunand CJ; Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, IL.
  • Huang M; Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, IL.
  • Fitzgerald-Miller L; Barbara Davis Center, University of Colorado School of Medicine, Aurora, CO.
  • Stowell D; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO.
  • Hinman RM; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO.
  • Wilson PC; Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, IL.
  • Gottlieb PA; Barbara Davis Center, University of Colorado School of Medicine, Aurora, CO.
  • Cambier JC; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO john.cambier@ucdenver.edu.
Diabetes ; 64(5): 1703-12, 2015 May.
Article em En | MEDLINE | ID: mdl-25524915
Although dogma predicts that under normal circumstances, potentially offensive autoreactive cells are silenced by mechanisms of immune tolerance, islet antigen-reactive B lymphocytes are known to play a crucial role in the development of autoimmunity in type 1 diabetes (T1D). Thus, participation of these cells in T1D may reflect escape from silencing mechanisms. Consistent with this concept, we found that in healthy subjects, high-affinity insulin-binding B cells occur exclusively in the anergic naive IgD(+), IgM(-) B-cell (BND) compartment. Antigen receptors expressed by these cells are polyreactive and have N-region additions, Vh usage, and charged complementarity-determining region 3 consistent with autoreactivity. Consistent with a potential early role in autoimmunity, these high-affinity insulin-binding B cells are absent from the anergic compartment of some first-degree relatives and all prediabetic and new-onset (<1 year) T1D patients tested, but return to normal levels in individuals diabetic for >1 year. Interestingly, these changes were correlated by transient loss of the entire BND compartment. These findings suggest that environmental events such as infection or injury may, by disrupting B-cell anergy, dispose individuals toward autoimmunity, the precise nature of which is specified by genetic risk factors, such as HLA alleles.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Estado Pré-Diabético / Linfócitos B / Anergia Clonal / Diabetes Mellitus Tipo 1 Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Diabetes Ano de publicação: 2015 Tipo de documento: Article País de publicação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Estado Pré-Diabético / Linfócitos B / Anergia Clonal / Diabetes Mellitus Tipo 1 Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Diabetes Ano de publicação: 2015 Tipo de documento: Article País de publicação: Estados Unidos