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Mannan‐Binding Lectin Inhibits Humoural Responses
Author(s) -
Ruseva M.,
Gajdeva M.,
Takahashi K.,
Ezekowitz A.,
Thiel S.,
Jensenius J. C.
Publication year - 2004
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.0300-9475.2004.01423an.x
Subject(s) - immunology , mannan binding lectin , hbsag , biology , immune system , antigen , complement system , lectin , glycoprotein , immunity , acquired immune system , hepatitis b virus , virus , microbiology and biotechnology
Chronic hepatitis B virus (HBV) infection affects about 200–400 million people worldwide and represents one of the leading causes for liver cirrhosis and hepatocellular carcinoma. Control over the HBV infection is achieved mainly by vaccination with Hepatitis B surface antigen (HBsAg). HBsAg contains N ‐linked glycosylation side and is recognized by both MBL‐A and MBL‐C in a Ca‐dependent manner. HbsAg–MBL complexes activate complement and may thus affect humoural immunity. To investigate the role of MBL in humoural responses to HBsAg, we immununized mice that lack both MBL‐A and MBL‐C proteins with soluble HBsAg. It has been shown that deficiencies in other complement components like C1q, C4 and C3 result in decreased antibody responses. However, MBL double KO animals mounted dramatically increased humoural responses. After priming, MBL double KOs mounted HbsAg‐specific IgM responses, which were threefold higher than WT controls. After boosting the HBsAg, total IgG was 10‐fold higher in MBL KO than in WT control animals. Similar to the response to HbsAg, other glycosylated soluble antigens (e.g. invertase) induced better humoural responses in MBL double KO animals, suggesting that MBL plays an important role in a negative feedback regulation of adaptive immunity. Reconstitution experiments with rMBL partially rescued the KO phenotype. We propose that the clearance of glycoprotein antigens in MBL KO is handled differently from the WT, resulting in better stimulation of humoural responses. Alternatively, glycoprotein‐Ag‐MBL‐rich complexes inhibit B‐cell responsiveness via putative MBL receptors.