@article{d363f6af6b494855a87351c62ed2940c,
title = "A novel role for caveolin-1 in B lymphocyte function and the development of thymus-independent immune responses",
abstract = "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 manner in 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 IgG3 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.",
keywords = "Antibody production, B lymphocytes, Caveolin-1",
author = "Medina, {Freddy A.} and Williams, {Terence M.} and Federica Sotgia and Tanowitz, {Herbert B.} and Lisanti, {Michael P.}",
note = "Funding Information: Recent evidence has shown that B-lymphocytes contain sphingolipid-and cholesterol-rich plasma membrane microdomains, termed lipid rafts. Located within lipid rafts are a number of tightly regulated molecules involved in B-lymphocyte signal transduction.1,2 Furthermore, it has been suggested that plasma membrane lipid rafts in B cells may play a role in antigen caveolin-1, B lymphocytes, antibody production internalization and processing.3 A lipid raft subset yet to be studied in B-lymphocytes are caveolae. There are different shapes and forms of caveolae found within cells, but they are most commonly described as flask-shaped invaginations (50–100 nm) found at the plasma membrane. Other forms of caveolae are observed as vesicles residing near the membrane, “grape-like” structures, tubules or flat patches within the plane of the plasma membrane.4 These structures were initially described by Yamada5 and Palade6 in the 1950s. They are most commonly found in fibroblasts, adipocytes, endothelial cells, type I pneumocytes, epithelial cells, smooth muscle and striated muscle cells. This work was supported by grants from the One of the major constituents of caveolae is the 21-24 kDa integral membrane protein, National Institutes of Health (NIH), and the caveolin-1. Together with the help of other components, such as cholesterol and American Heart Association (AHA). We glycosphingolipids, caveolin-1 (Cav-1) drives formation of the caveolar lipid raft thank expert dermatopathologist Dr. Steve microdomains.7-9 Previous studies in our lab have shown that Cav-1-/- mice lack caveolae McClain (Montefiore Medical Center) for his suggesting that Cav-1 is necessary for the formation of caveolae in cells.7 It is thought that assistance. Cav-1 can function as a molecular platform that concentrates signaling proteins and thereby increases the effectiveness of intracellular signaling events.10There are a number of lipid-anchored, integral, and soluble signaling proteins that are recruited to caveolae and interact with Cav-1.11-13The caveolin-1 scaffolding domain (residues 82-101) mediates {\textcopyright}2006 LANDES BIOSCIENCEthese protein-protein interactions.10Proteins that interact with and bind Cav-1 have been found to have characteristic caveolin binding motifs (ΦXXXXΦXXΦ and ΦXΦXXXXΦ, where Φ represents an aromatic amino acid).14The scaffolding domain functions by acting as a platform that various proteins bind to while simultaneously inhibiting or enhancing the protein{\textquoteright}s signaling activity. Although the function of caveolae remains unknown, they have been implicated in various cellular processes such as cholesterol and triglyceride home-ostasis, cell cycle regulation, apoptosis, vesicular trafficking, and signal transduction.4,15-18",
year = "2006",
month = aug,
day = "15",
doi = "10.4161/cc.5.16.3132",
language = "English (US)",
volume = "5",
pages = "1865--1871",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "16",
}