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J Immunol ; 169(6): 2971-8, 2002 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-12218111

RESUMO

Natural Abs (NAbs) are Igs present in the serum and body fluids of healthy vertebrate animals, without any previous intentional immunization. NAbs often exhibit autoreactivity but also play an essential role in immunity, being a first line of defense against infectious microorganisms. We have previously analyzed the natural serum IgM Ab repertoire of normal mice, characterizing their reactivity with hundreds/thousands of self Ags; a significant similarity among different individuals was observed, and it was found that many reactivities of NAbs stably kept during adulthood were established early in life, implicating that period as a critical time window in the physiology of NAb repertoire selection. In the work reported here, experiments were conducted to address the role of normal lymphocyte ontogeny to the formation and stability of adult NAb repertoire. The massive destruction of the lymphoid system was promoted in adult mice with gamma-irradiation, and regeneration of hemopoietic tissues was granted by bone marrow or fetal liver inoculum. NAb repertoire regeneration was followed for 60 days after gamma-irradiation in bone marrow or fetal liver chimeric animals. The analysis of serum IgM reactivity with hundreds/thousands of self Ags showed that the NAb repertoire regenerated most of its original format after massive destruction of lymphoid compartments, characterizing autoreactive repertoire selection as a robust biological process. The data also show that regeneration of the NAb repertoire occurred similarly in fetal liver and bone marrow chimeras, although the latter animals poorly reconstituted their CD5(+) B1 cell compartment, suggesting that B1 cells are not essential for natural Ab regeneration.


Assuntos
Especificidade de Anticorpos , Autoantígenos/metabolismo , Sítios de Ligação de Anticorpos , Imunoglobulinas/biossíntese , Depleção Linfocítica , Tecido Linfoide/efeitos da radiação , Envelhecimento/genética , Envelhecimento/imunologia , Animais , Especificidade de Anticorpos/genética , Autoantígenos/imunologia , Sítios de Ligação de Anticorpos/genética , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Células da Medula Óssea/efeitos da radiação , Transplante de Medula Óssea , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Transplante de Tecido Fetal/imunologia , Imunidade Inata/genética , Imunoglobulina M/biossíntese , Imunoglobulina M/sangue , Imunoglobulinas/sangue , Imunoglobulinas/metabolismo , Fígado/imunologia , Fígado/metabolismo , Depleção Linfocítica/métodos , Tecido Linfoide/imunologia , Tecido Linfoide/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Músculo Esquelético/imunologia , Músculo Esquelético/metabolismo , Quimera por Radiação/imunologia
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