Mannose-binding lectin (MBL), a pattern recognition innate immune molecule, selectively binds distinct chemical patterns, including carbohydrates expressed on Group B streptococcus (GBS). MBL interacts with IgM, resulting in the activation of MBL-associated serine proteases (MASPs), thus is initiating a lectin complement pathway. Complement proteins and IgM modulate production of antigen specific antibody. In this study, we investigated the relative effect of MBL in antibody response against tetanus toxoid-conjugated GBS polysaccharide vaccines (GBS PS-TT) by comparing wild type and null mice for MBL, complement 3 (C3), IgM, MBL/C3, and MBL/IgM. We found that GBS PS specific IgG response was upregulated in MBL deficient mice following immunization with GBS PS-TT but not GBS PS. B1 cells were expanded in peritonium but not in spleen of MBL null mice. The mechanisms of heightened IgG response in MBL null mice were related to C3, and share the same pathway with IgM.