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Role of distinct immune components in the radiation-induced abrogation of systemic lupus erythematosus development in mice

Disciplina de Imunologia, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, Escola Paulista de Medicina, Rua Botucatu, São Paulo, Brazil, ronnibrito@ ecb.epm.br

B.H.P. De Lorenzo

Disciplina de Imunologia, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, Escola Paulista de Medicina, Rua Botucatu, São Paulo, Brazil

P. Xander

Disciplina de Imunologia, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, Escola Paulista de Medicina, Rua Botucatu, São Paulo, Brazil

L.C. Godoy

Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, 364 Plantation St. Worcester-MA, 01604, USA

J.D. Lopes

Disciplina de Imunologia, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, Escola Paulista de Medicina, Rua Botucatu, São Paulo, Brazil

N.P. da Silva

Disciplina de Reumatologia, Departamento de Medicina, Universidade Federal de São Paulo, Escola Paulista de Medicina, Pedro de Toledo, São Paulo, Brazil

S.C. Sampaio

Laboratório de Patofisiologia, Instituto Butantã, Av. Vital Brasil, São Paulo, Brazil

M. Mariano

Disciplina de Imunologia, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, Escola Paulista de Medicina, Rua Botucatu, São Paulo, Brazil

The New Zealand Black x New Zealand White F1 [(NZB/NZW) F1] mouse develops an autoimmune condition resembling aspects of human systemic lupus erythematosus (SLE). We investigated the effects of a novel prophylactic thoraco-abdominal gamma irradiation protocol on the onset and evolution of lupus in these animals. Survival of irradiated mice was higher when compared with nonirradiated mice. Kidney lesions were milder and autoantibody levels were lower in irradiated mice. To identify possible mechanisms involved in the radiation-induced improvement of disease, distinct components of humoral and cellular immune responses were evaluated. Because B-1 cells are known to be involved in various autoimmune diseases, we investigated the participation of these cells in SLE progression. Unexpectedly, B-1 cells were not depleted in (NZB/NZW) F1, even after several rounds of irradiation. No alterations were found in viability and physiology of B-1 cells in SLE animals with the exception of constitutive overexpression of the anti-apoptotic molecule Bcl-2, which may account for the observed radioresistance. Thus, a role for B-1 cells in murine SLE cannot be excluded, since the irradiation protocol did not effectively eliminate these cells. Additionally, we demonstrate a marked delay in the ability of splenocytes to repopulate the spleen after irradiation in (NZB/NZW) F1, in contrast to leucocytes in other cellular compartments. The implications of these findings for the fate of SLE in this model are discussed. Lupus (2007) 16, 947—954.

Key Words: B-1 cells • irradiation • systemic lupus erythematosus

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