An intrinsic B cell defect is required for the production of autoantibodies in the lpr model of murine systemic autoimmunity.
Mice homozygous for the gene lpr develop marked lymphadenopathy and a spectrum of autoantibodies closely resembling that of human systemic lupus erythematosus. The unusual T cell phenotype of the expanded lymphocyte population and the T-dependence of several antibodies in this strain have suggested that primary T cell abnormalities underlie the autoimmune syndrome. Using double chimeras, we now show that expression of the lpr gene in B cells is absolutely necessary for autoantibody production. Combinations of anti-Thy 1.2 + C' treated bone marrow from congenic strains of C57BL/6 mice, differing only at the immunoglobulin heavy chain (Igh) and lpr loci, were transferred into lethally irradiated B6/lpr mice. Double chimerism was documented by allotype-specific surface IgD and IgM immunofluorescence assay of peripheral blood and by allotype-specific enzyme-linked immunosorbent assay for total IgM in serum. Despite the presence of both +/+ and lpr B cells, IgM and IgG2a anti-chromatin as well as IgM anti-IgG were entirely the products of lpr B cells. Total serum IgG2a and IgG1 were also dominated by the lpr phenotype but not to the same extent. A similar experiment using B6/lpr-Igha recipients confirmed these findings. Additional experiments in which B6/lpr recipients were infused with ratios of donor bone marrow favoring B6.C20 +/+ over B6/lpr showed that even though +/+ B cells were overrepresented, autoantibodies were only of the lpr allotype. In addition, in the presence of lpr B cells, normal B cells showed little response to an exogenous, T cell-dependent antigen. The data thus indicate that lpr B cells manifest an intrinsic abnormality which is essential for autoantibody production in the lpr model.
Sobel
E S
ES
Department of Microbiology/Immunology, University of North Carolina, Chapel Hill 27599.
Katagiri
T
T
Katagiri
K
K
Morris
S C
SC
Cohen
P L
PL
Eisenberg
R A
RA
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D016026:Bone Marrow Transplantation; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D011828:Radiation Chimera; D013601:T-Lymphocytes / Q000276:immunology; D014301:Trinitrobenzenes / Q000276:immunology
D001323:Autoantibodies; D014301:Trinitrobenzenes