Impaired antibody response to group B streptococcal type III capsular polysaccharide in C3- and complement receptor 2-deficient mice.
Group B Streptococcus (GBS) is the foremost bacterial cause of serious neonatal infections. Protective immunity to GBS is mediated by specific Abs to the organism's capsular polysaccharide Ags. To examine the role of complement in the humoral immune response to type III GBS capsular polysaccharide (III-PS), mice deficient in C3 or in CD21/CD35 (i.e., complement receptors 1 and 2; CR1/CR2) were immunized with III-PS. Mice deficient in C3 or Cr2 had an impaired primary immune response to III-PS. The defective response was characterized by low IgM levels and the lack of an isotype switch from IgM to IgG Ab production. Compared with wild-type mice, C3- and Cr2-deficient mice exhibited decreased uptake of III-PS by follicular dendritic cells within the germinal centers and impaired localization of III-PS to the marginal zone B cells. Complement-dependent uptake of capsular polysaccharide by marginal zone B cells appears necessary for an effective immune response to III-PS. The normal immune response in wild-type mice may require localization of polysaccharide to marginal zone B cells with subsequent transfer of the Ag to follicular dendritic cells.
Pozdnyakova
Olga
O
Department of Pathology, Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA.
Guttormsen
Hilde-Kari
HK
Lalani
Farah N
FN
Carroll
Michael C
MC
Kasper
Dennis L
DL
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003176:Complement C3 / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D020566:Dendritic Cells, Follicular / Q000276:immunology / Q000378:metabolism; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000097:blood; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011135:Polysaccharides, Bacterial / Q000276:immunology* / Q000378:metabolism; D017464:Receptors, Complement 3d / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D013292:Streptococcus agalactiae / Q000276:immunology*
D000907:Antibodies, Bacterial; D003176:Complement C3; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011135:Polysaccharides, Bacterial; D017464:Receptors, Complement 3d; C032263:streptococcal polysaccharide type III group B