B-lymphocyte depletion reduces skin fibrosis and autoimmunity in the tight-skin mouse model for systemic sclerosis.
Systemic sclerosis (scleroderma) is an autoimmune disease characterized by excessive extracellular matrix deposition in the skin. A direct role for B lymphocytes in disease development or progression has remained controversial, although autoantibody production is a feature of this disease. To address this issue, skin sclerosis and autoimmunity were assessed in tight-skin mice, a genetic model of human systemic sclerosis, after circulating and tissue B-cell depletion using an anti-mouse CD20 monoclonal antibody before (day 3 after birth) and after disease development (day 56). CD20 monoclonal antibody treatment (10 to 20 microg) depleted the majority (85 to 99%) of circulating and tissue B cells in newborn and adult tight-skin mice by days 56 and 112, respectively. B-cell depletion in newborn tight-skin mice significantly suppressed (approximately 43%) the development of skin fibrosis, autoantibody production, and hypergammaglobulinemia. B-cell depletion also restored a more normal balance between Th1 and Th2 cytokine mRNA expression in the skin. By contrast, B-cell depletion did not affect skin fibrosis, hypergammaglobulinemia, and autoantibody levels in adult mice with established disease. Thereby, B-cell depletion during disease onset suppressed skin fibrosis, indicating that B cells contribute to the initiation of systemic sclerosis pathogenesis in tight-skin mice but are not required for disease maintenance.
Hasegawa
Minoru
M
Department of Dermatology, Kanazawa University Graduate School of Medical Science, Japan.
Hamaguchi
Yasuhito
Y
Yanaba
Koichi
K
Bouaziz
Jean-David
JD
Uchida
Junji
J
Fujimoto
Manabu
M
Matsushita
Takashi
T
Matsushita
Yukiyo
Y
Horikawa
Mayuka
M
Komura
Kazuhiro
K
Takehara
Kazuhiko
K
Sato
Shinichi
S
Tedder
Thomas F
TF
D000375:Aging / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology*; D018951:Antigens, CD20 / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D012595:Scleroderma, Systemic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012867:Skin / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology
D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D001323:Autoantibodies; D016207:Cytokines; D012333:RNA, Messenger