Conventional B cells, not B-1 cells, are responsible for producing autoantibodies in lpr mice.
Mice homozygous for the lpr gene develop autoantibodies and polyclonal B cell activation similar to what is seen in human systemic lupus erythematosus patients. We have previously shown that an lpr-specific intrinsic B cell defect was necessary for autoantibody production in this model. In the current study, we have further defined these autoantibody-producing B cells. Two major subsets of B cells have been described. B-1 cells (CD5+ B cells) can be distinguished from conventional B cells on the basis of phenotype, cytokine secretion, gene expression, anatomical location, and function. In addition, B-1 cells have been implicated in autoimmunity in several murine and human studies. To address the question of which B cell subset produces autoantibodies in lpr mice, we used immunoglobulin heavy chain (Igh) allotype-marked peritoneal (B-1 cell source) and bone marrow (conventional B cell source) cells from lpr mice to establish B cell chimeras. We used two general approaches. In one, we reconstituted sublethally irradiated mice with B-1 cells of one allotype and bone marrow cells of another allotype. In the second method, we suppressed endogenous B cells in neonatal mice with allotype-specific anti-IgM antibody, and injected peritoneal cells of another allotype. After antibody treatment was stopped, the mouse's conventional B cells recovered, but the B-1 subset was only reconstituted by the donor. In both types of chimeras, antichromatin, rheumatoid factor, and anti-single stranded DNA (ssDNA) autoantibodies were produced by the conventional B cell bone marrow source. In addition, an age-related decrease in peritoneal B-1 cells was seen, even in unmanipulated lpr mice. These data show that lpr B-1 cells are not important producers of autoantibodies. Conventional B cells are the source of autoantibodies directed at chromatin, ssDNA, and IgG.
Reap
E A
EA
Department of Medicine, University of North Carolina, Chapel Hill 27599-7280.
Sobel
E S
ES
Cohen
P L
PL
Eisenberg
R A
RA
D000375:Aging; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011828:Radiation Chimera
D001323:Autoantibodies