Altered blood B lymphocyte homeostasis in systemic sclerosis: expanded naive B cells and diminished but activated memory B cells.
OBJECTIVE
To determine phenotypic and functional abnormalities of blood B cell subsets in patients with systemic sclerosis (SSc).


METHODS
Cell surface marker expression was determined by flow cytometry. Spontaneous apoptosis was evaluated by annexin V expression with flow cytometric analysis. IgG production by isolated IgD- memory B cells was examined by enzyme-linked immunosorbent assay.


RESULTS
The numbers of blood CD27- naive B cells from SSc patients were increased compared with normal control cells, while memory B cells expressing medium levels of CD27 and plasmablasts expressing high levels of CD27 were reduced. In contrast, plasmablasts were the predominant population in patients with systemic lupus erythematosus (SLE). Memory B cells in SSc showed increased expression of activation markers, including CD80, CD86, and CD95, relative to normal controls. Consistent with CD95 up-regulation, SSc memory B cells exhibited augmented spontaneous apoptosis after 24-hour incubation; augmented apoptosis may explain the reduced memory B cell number. Nonetheless, isolated IgD- SSc memory B cells treated with stimuli had an enhanced ability to produce IgG. Furthermore, expression of CD19, a critical signal transduction molecule of B cells that regulates autoantibody production, was significantly increased in memory B cells as well as in naive B cells in SSc. In contrast, CD19 expression was decreased in SLE B cells.


CONCLUSIONS
SSc patients have distinct abnormalities of blood homeostasis and B cell compartments, characterized by expanded naive B cells and activated but diminished memory B cells. Our results suggest that CD19 overexpression in SSc memory B cells is related to their hyperreactivity.
Sato
Shinichi
S
Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan. s-sato@med.kanazawa-u.ac.jp
Fujimoto
Manabu
M
Hasegawa
Minoru
M
Takehara
Kazukiko
K
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D005260:Female; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D006942:Hypergammaglobulinemia / Q000276:immunology; D007074:Immunoglobulin G / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000276:immunology*; D019014:fas Receptor / Q000378:metabolism
D015703:Antigens, CD; D018941:Antigens, CD19; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D019014:fas Receptor