Autoantibody repertoire analysis in normal and lupus-prone mice
|Published in||Journal of Autoimmunity. 1989, vol. 2, no. 5, p. 657-674|
|Abstract||We have analyzed at the clonal level (limiting dilution assay) the repertoire of lipopolysaccharide (LPS)-responsive murine B cells committed to the production of autoantibodies characteristic of systemic lupus erythematous (SLE), i.e. anti-single-stranded DNA (ssDNA), anti-double-stranded DNA, anti-Sm and rheumatoid factors (RF). Our results demonstrated that: (1) the frequency of precursor B cells producing each lupus autoantibody (approximately 1 in every 100-400 LPS-responding B cell) was similar in two non-autoimmune (C57BL/6 and BALB/c) and four SLE-prone (NZB, (NZB x NZW)F1, MRL/MpJ and BXSB/MpJ) mice despite the marked differences in autoimmune responses in the different SLE-prone mice, and (2) the relative frequency of autoantibody-secreting precursor B cells was constant throughout life, and equally distributed among activated and resting B-cell populations and among B cells from the peritoneal cavity and spleen. The lack of association of anti-ssDNA secretion with anti-Sm or RF secretion in cultures set up with a smaller number of B cells ruled out the possibility that the similar frequency of different autoantibody-secreting cell precursors is due to the poly-specificity of IgM autoantibodies. Notably, the frequencies of autoantibody-secreting precursor cells were significantly lower, approximately 4 and 10 times, than those of anti-tetanus toxoid and anti-dinitrophenyl antibody-producing precursor B cells, respectively. The similar frequency of precursor B cells producing four different lupus autoantibodies on the one hand and the considerable variation in each autoimmune response among SLE-prone mice on the other, support the hypothesis that specific stimulatory mechanisms may govern each autoimmune response in different SLE strains of mice.|
|Keywords||Animals — Animals, Newborn/immunology — Autoantibodies/ analysis/immunology — B-Lymphocytes/ immunology — Cell Differentiation — Clone Cells/immunology — Disease Models, Animal — Female — Lipopolysaccharides/pharmacology — Lupus Erythematosus, Systemic/genetics/ immunology — Lymphocyte Activation/drug effects — Mice — Mice, Inbred NZB/ immunology — Mice, Inbred Strains/ immunology — Mice, Mutant Strains/ immunology — Models, Biological — Peritoneal Cavity/pathology — Rats — Rats, Inbred Strains/immunology — Spleen/pathology|
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