Phenotypic abnormalities of splenic and bone marrow B cells in lpr and gld mice.
Mice homozygous for the mutant Fas gene lpr develop generalized lymphoproliferation and produce autoantibodies resembling those found in human SLE. We have previously shown that these autoantibodies are produced by B2 cells rather than B1 cells and that the autoantibody- producing B cells are intrinsically abnormal. We investigated further the lpr B cell with a large panel of antibodies to B-cell surface markers to identify phenotypic abnormalities. B cells from spleen and bone marrow of age-matched congenic mice differing only at the lpr locus were examined by flow cytometry. Two consistent phenotypic differences were identified. First, spleen cells from older lpr mice had an increase in the number and percentage of IgM+ B cells expressing low levels of CD23. Second, lpr bone marrow had decreased numbers of B220hiIgM+-syndecan-1+CD23+ B cells. All other markers tested, except the previously identified modest increase of Ia on lpr spleen cells, showed no consistent differences. B cells from gld mice showed the same phenotypic abnormalities as those from lpr. Compared to T cells, the relative paucity of cell surface marker differences between lpr and +/+ B cells suggests that B cells may have fewer regulatory mechanisms to silence autoreactive specificities. The phenotypic differences identified may provide clues to the mechanism of autoantibody production in lpr mice, while the overwhelming phenotypic similarity between lpr and +/+ B cells suggests that the major abnormality of lpr B cells may lie in their specificity, that is, in their inability to delete autoreactive subsets.
Reap
E A
EA
Department of Medicine, University of North Carolina, Chapel Hill, 27599-7280, USA.
Piecyk
M L
ML
Oliver
A
A
Sobel
E S
ES
Waldschmidt
T
T
Cohen
P L
PL
Eisenberg
R A
RA
D000818:Animals; D001402:B-Lymphocytes / Q000145:classification / Q000276:immunology*; D001853:Bone Marrow / Q000473:pathology*; D007075:Immunoglobulin M / Q000032:analysis; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000235:genetics; D018655:Lymphocyte Count; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017455:Receptors, IgE / Q000235:genetics; D013154:Spleen / Q000473:pathology*
D007075:Immunoglobulin M; D017455:Receptors, IgE; D017493:Leukocyte Common Antigens