In vitro and in vivo functional analysis of CD5+ and CD5- B cells of autoimmune NZB x NZW F1 mice.
Polyclonal B cell activation has been thought to play the critical role in production of autoantibodies, and possible activation of autoreactive T cells in murine lupus, especially abnormal expansion of CD5+ B cells, is one of the characteristic findings in these mice. The aim of this study was to investigate further the characteristics and function of CD5+ and CD5- B cells. Both CD5+ and CD5- B cells were isolated for in vitro autoantibody production, cytokine expression and in vivo anti-DNA antibody production with reconstitution of severe combined immunodeficient (SCID) mice. The data showed: (i) both CD5+ and CD5- B cells produced a high level of anti-DNA antibody after stimulation with lipopolysaccharide (LPS) plus IL-5; (ii) both peritoneal CD5+ and CD5- B cells expressed a high level of IL-10 mRNA after stimulation with LPS, while in contrast CD5- B cells of non-autoimmune BALB/c mice did not express IL-10 mRNA after stimulation; (iii) SCID mice reconstituted with either CD5+ or CD5- B cells all produced significant levels of anti-DNA antibodies in vivo and manifested with proteinuria. These data suggest both CD5+ and CD5- B cells play important roles in polyclonal B cell activation and subsequent autoantibody production. Generalized polyclonal B cell activation, instead of expanding a certain subpopulation of B cells, contributed to the pathogenesis of autoimmunity in murine lupus.
Ye
Y L
YL
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, R.O.C.
Chuang
Y H
YH
Chiang
B L
BL
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001327:Autoimmune Diseases; D001402:B-Lymphocytes / Q000502:physiology*; D018956:CD5 Antigens / Q000502:physiology*; D002469:Cell Separation; D017931:DNA Primers; D005260:Female; D016753:Interleukin-10 / Q000096:biosynthesis; D008070:Lipopolysaccharides; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D016513:Mice, SCID; D011507:Proteinuria / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D016511:Severe Combined Immunodeficiency / Q000378:metabolism
D000974:Antibodies, Antinuclear; D018956:CD5 Antigens; D017931:DNA Primers; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10