Autoantibody repertoire analysis in normal and lupus-prone mice.
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.
Starobinski
M
M
Department of Pathology, University of Geneva, Switzerland.
Lacour
M
M
Reininger
L
L
Izui
S
S
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002999:Clone Cells / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008814:Mice, Inbred NZB / Q000276:immunology*; D008815:Mice, Inbred Strains / Q000276:immunology*; D008817:Mice, Mutant Strains / Q000276:immunology*; D008954:Models, Biological; D010529:Peritoneal Cavity / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains / Q000276:immunology; D013154:Spleen / Q000473:pathology
D001323:Autoantibodies; D008070:Lipopolysaccharides