B cells lacking RP105, a novel B cell antigen, in systemic lupus erythematosus.
OBJECTIVE
RP105 is a leucine-rich repeat (LRR) protein found on all mature mouse B cells. Its function is poorly defined, although it has been suggested that RP105 activates B cells to make them resistant to apoptosis. The human homolog of RP105 has been reported, but knowledge of its function is limited. We explored the expression and the function of the human homolog of murine RP105 on B cells in patients with systemic lupus erythematosus (SLE).


METHODS
The expression of RP105 and various markers on B cells in patients with SLE was analyzed using monoclonal antibodies and flow cytometry. Susceptibility to corticosteroid-induced apoptosis was examined by annexin V binding, and the production of immunoglobulin by RP105-negative B cells was examined by intracellular staining of IgG.


RESULTS
As in mice, virtually all B cells in the peripheral blood of normal humans expressed the RP105 molecule. However, a significant proportion of circulating B cells (15.9%) in SLE patients were RP105 negative. Serial analyses of B cells in 7 SLE patients revealed that RP105-negative B cells markedly decreased in parallel with a reduction in disease activity (from 35.2% to 3.3%; P = 0.000003). The SLE Disease Activity Index and serum levels of IgG also correlated with the percentage of RP105-negative B cells. The phenotype of RP105-negative B cells was defined as CD95-positive, CD86-positive, CD38-bright, IgD-negative, IgM-dull, indicating that the cells were highly activated, as further suggested by the detection of intracellular IgG. RP105-negative B cells were clearly distinct from CD5-positive B1 cells. In vitro experiments indicated that RP105-negative B cells were susceptible to corticosteroid-induced apoptosis.


CONCLUSIONS
These findings suggest that loss of RP105 is associated with B cell activation and increased disease activity in SLE patients.
Koarada
S
S
Department of Internal Medicine, Saga Medical School, Nabeshima, Japan.
Tada
Y
Y
Ushiyama
O
O
Morito
F
F
Suzuki
N
N
Ohta
A
A
Miyake
K
K
Kimoto
M
M
Nagasawa
K
K
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD; D000954:Antigens, Surface / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008565:Membrane Proteins / Q000032:analysis*; D051379:Mice; D010641:Phenotype; D019014:fas Receptor / Q000235:genetics
D000305:Adrenal Cortex Hormones; D015703:Antigens, CD; D000954:Antigens, Surface; C092722:CD180 protein, human; C490500:Ly78 protein, mouse; D008565:Membrane Proteins; D019014:fas Receptor