TY - JOUR
T1 - Phenotypic abnormalities of splenic and bone marrow B cells in lpr and gld mice
AU - Reap, Elizabeth A.
AU - Piecyk, Monica L.
AU - Oliver, Alyce M.
AU - Sobel, Eric S.
AU - Waldschmidt, Thomas
AU - Cohen, Philip L.
AU - Eisenberg, Robert A.
N1 - Funding Information:
We thank Becky Rapoport and Anne Wolthusen for their help with the mice, Dr. Ralph Sanderson for his generous gift of syndecan-1 antibody, and Dr. Larry Arnold for assistance in flow cytometric analysis. This work was supported by NIH Grants R01AR40620, R01AR33887, R01AR26574, R01AR34156, P50AR42573, T32AR07416, P60AR30701, and R29AI31265 (T.W.).
PY - 1996
Y1 - 1996
N2 - 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 B220(h1) IgM+-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. E 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.
AB - 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 B220(h1) IgM+-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. E 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.
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U2 - 10.1006/clin.1996.0004
DO - 10.1006/clin.1996.0004
M3 - Article
C2 - 8599880
AN - SCOPUS:0029970275
SN - 0090-1229
VL - 78
SP - 21
EP - 29
JO - Clinical Immunology and Immunopathology
JF - Clinical Immunology and Immunopathology
IS - 1
ER -