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Titolo:
Genetic dissection of B cell traits in New Zealand black mice. The expanded population of B cells expressing up-regulated costimulatory molecules shows linkage to Nba2
Autore:
Wither, JE; Paterson, AD; Vukusic, B;
Indirizzi:
Toronto Western Hosp, Toronto Hosp, Res Inst, Arthrit Ctr Excellence, Toronto, ON M5T 2S8, Canada Toronto Western Hosp Toronto ON Canada M5T 2S8 oronto, ON M5T 2S8, Canada Ctr Addict & Mental Hlth, Clarke Div, Neurogenet Sect, Toronto, ON, CanadaCtr Addict & Mental Hlth Toronto ON Canada net Sect, Toronto, ON, Canada Univ Toronto, Dept Immunol, Toronto, ON, Canada Univ Toronto Toronto ON Canada oronto, Dept Immunol, Toronto, ON, Canada Univ Toronto, Dept Med, Toronto, ON, Canada Univ Toronto Toronto ON Canada iv Toronto, Dept Med, Toronto, ON, Canada Univ Toronto, Dept Psychiat, Toronto, ON, Canada Univ Toronto Toronto ON Canada ronto, Dept Psychiat, Toronto, ON, Canada
Titolo Testata:
EUROPEAN JOURNAL OF IMMUNOLOGY
fascicolo: 2, volume: 30, anno: 2000,
pagine: 356 - 365
SICI:
0014-2980(200002)30:2<356:GDOBCT>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
SYSTEMIC LUPUS-ERYTHEMATOSUS; TUMOR-NECROSIS-FACTOR; CONGENIC MOUSE STRAINS; AUTOANTIBODY PRODUCTION; AUTOIMMUNE-DISEASE; FACTOR-ALPHA; SUSCEPTIBILITY; ACTIVATION; NEPHRITIS; NZB;
Keywords:
rodent; B lymphocyte; lupus; autoimmunity; costimulatory molecule;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Wither, JE Toronto Western Hosp, Toronto Hosp, Res Inst, Arthrit Ctr Excellence, FP1-224,399 Bathurst St, Toronto, ON M5T 2S8, Canada Toronto WesternHosp FP1-224,399 Bathurst St Toronto ON Canada M5T 2S8
Citazione:
J.E. Wither et al., "Genetic dissection of B cell traits in New Zealand black mice. The expanded population of B cells expressing up-regulated costimulatory molecules shows linkage to Nba2", EUR J IMMUN, 30(2), 2000, pp. 356-365

Abstract

B cell abnormalities are a prominent feature of the immunologic derangement in NZB and NZB/W mice. We recently demonstrated that these mice have an increased proportion of splenic B cells expressing B7.1 and elevated levels of B7.2 and ICAM-1 that possess the characteristics of marginal zone B cells (CD23(low/-) CD5(-) CD44(hi) CD24(hi) IgD(-/low) IgM(hi)) and are found as early as 4-6 weeks of age. These findings suggest that activated B cells in NZB and NZB/W mice could serve a costimulatory function leading to activation of autoreactive T cells. However, it remains unclear whether there isany association between B abnormalities and nephritis in these mice. Here we have used genetic mapping techniques to address this issue. We show thatincreases in the proportion of B cells expressing costimulatory molecules,serum IgM levels, the number of IgM ELISpots, and IgG anti-single-stranded(ss) DNA antibody production, are significantly associated with a chromosomal region that overlaps with Nba2, a genetic locus previously linked to nephritis. Based on these findings we propose that immune mechanisms leading to polyclonal B cell activation and up-regulation of costimulatory molecules in these mice play a central role in the loss of tolerance that leads to production of pathogenic autoantibodies.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 23:13:35