The immature B-cell subpopulation with low RAG1 expression is increased in the autoimmune New Zealand Black mouse.
Receptor editing is believed to play a critical role in immunological tolerance by altering the specificity of autoreactive B cells that emerge in the bone marrow. To study whether receptor editing is altered in autoimmune disease, recombination activation gene 1 (rag1) transcription in B cells from New Zealand Black (NZB) mice was examined by introducing a GFP gene at the rag1 locus. Female NZB(RAG1-GFP) mice generated autoantibodies and glomerular immune complexes. NZB(RAG1-GFP) mice did not display increased RAG1-GFP signal in B-1 and B-2 cells from the spleen and peritoneal cavity even following in vitro stimulation compared with C57BL/6(RAG1-GFP) control mice. The early B cells in the bone marrow were classified into RAG1-GFP(-) and RAG1-GFP(+) subpopulations. The RAG1-GFP(-) immature B-cell population was in the minority in C57BL/6(RAG1-GFP) mice but was markedly increased in NZB(RAG1-GFP) mice. RAG1-GFP(-) immature B cells from NZB(RAG1-GFP) mice differentiated into anti-dsDNA Ab-producing cells after stimulation by LPS in vitro. RAG1-GFP(-) immature B cells from NZB(RAG1-GFP) mice displayed a different expression profile of transcription factors required for receptor editing, including pax5 and irf4, in comparison with the RAG1-GFP(+) immature B-cell population. In conclusion, the early B-cell subpopulation, which exhibits low RAG1 expression and presumably concomitantly low receptor editing, was found to be increased in NZB mice.
Toda
Teppei
T
Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Kitabatake
Masahiro
M
Igarashi
Hideya
H
Sakaguchi
Nobuo
N
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity / Q000276:immunology; D005260:Female; D055879:Gene Knock-In Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D054448:Precursor Cells, B-Lymphoid / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D001323:Autoantibodies; D018398:Homeodomain Proteins; D008070:Lipopolysaccharides; C064658:RAG-1 protein; D049452:Green Fluorescent Proteins