A novel role for caveolin-1 in B lymphocyte function and the development of thymus-independent immune responses.
Caveolin-1 (Cav-1) functions as a scaffold or platform for many molecules involved in signal transduction. However, the expression and function of Cav-1 in the immune system has been controversial. Here, we show that Cav-1 mRNA and protein is indeed expressed in murine B-lymphocytes in a regulated mannerin response to LPS. Cav-1 deficient mice displayed reduced levels of antibody in their serum. In order to examine the role of Cav-1 in the development of immunoglobulin-mediated immune responses, we immunized wild-type and Cav-1 deficient mice with thymus-dependent and thymus independent antigens. Our results show that Cav-1 deficient mice have a normal response to thymus-dependent antigens, but have a reduced response to both type I and type II thymus independent antigens. However, lymphocyte populations in the spleen and peritoneum were not altered and no changes were observed in splenic architecture. Caveolin-1 deficient B-lymphocytes did not display altered proliferation in response to different stimuli. However, we found that Cav-1 deficient B cells have reduced IgG(3) secretion in vitro in response to LPS. Finally, we also demonstrate that human plasma cells (mature B lymphocytes) express Cav-1 in vivo. Taken, together these results provide convincing evidence for the expression of Cav-1 in activated B-lymphocytes and demonstrate a role for Cav-1 in the development of thymus-independent immune responses.
Medina
Freddy A
FA
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA.
Williams
Terence M
TM
Sotgia
Federica
F
Tanowitz
Herbert B
HB
Lisanti
Michael P
MP
D000818:Animals; D000906:Antibodies / Q000097:blood; D000955:Antigens, T-Independent / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D021941:Caveolae / Q000276:immunology; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005362:Ficoll / Q000031:analogs & derivatives / Q000276:immunology; D005786:Gene Expression Regulation; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D007074:Immunoglobulin G / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014301:Trinitrobenzenes / Q000276:immunology
D000906:Antibodies; D000955:Antigens, T-Independent; D051242:Caveolin 1; D006241:Haptens; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C020529:TNP-ficoll; D014301:Trinitrobenzenes; C054401:trinitrophenyl keyhole limpet hemocyanin; C048761:trinitrophenyl-lipopolysaccharide; D005362:Ficoll; D006433:Hemocyanins