PHENOTYPIC ABNORMALITIES OF SPLENIC AND BONE-MARROW B-CELLS IN LPR AND GLD MICE

Mice homozygous for the mutant Fas gene lpr develop generalized lympho proliferation and produce autoantibodies resembling those found in hum an SLE, We have previously shown that these autoantibodies are produce d 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 id entify phenotypic abnormalities, B cells from spleen and bone marrow o f age-matched congenic mice differing only at the lpr locus were exami ned by flow cytometry. Two consistent phenotypic differences were iden tified, 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(+)-synd ecan-1(+)CD23(+) B cells. All other markers tested, except the previou sly identified modest increase of Ia on lpr spleen cells, showed no co nsistent differences, B cells from gld mice showed the same phenotypic abnormalities as those from lpr. Compared to T cells, the relative pa ucity of cell surface marker differences between lpr and +/+ B cells s uggests that B cells may have fewer regulatory mechanisms to silence a utoreactive specificities. The phenotypic differences identified may p rovide clues to the mechanism of autoantibody production in lpr mice, while the overwhelming phenotypic similarity between lpr and +/+ B cel ls suggests that the major abnormality of lpr B cells may lie in their specificity, that is, in their inability to delete autoreactive subse ts. (C) 1996 Academic Press, Inc.