Human immune response to pneumococcal polysaccharides:Complement-mediated localization preferentially on CD21-positive splenic marginal zone B cells and follicular dendritic cells

A functionally intact spleen with a marginal zone, containing B cells with high density of surface C3d-receptors (CD21), is essential for the ability to induce a primary immune response to thymus-independent type 2 (TI-2) antigens. Main representatives of natural TI-2 antigens are capsular pneumococcal polysaccharides (PPSs). In this study the localization of different types of PPS antigen is determined in human spleen tissue. Our findings indicate that a main type of TI-2 antigen, PPS, localizes preferentially in the marginal zone. PPSs show co-localization with C3, presumably C3d, at the surface of strongly CD21+ B cells equipped for rapid activation. This enables a rapid primary humoral response. The other main PPS localization at follicular dendritic cells in germinal centers, relevant for isotype switching of anti-PPS antibodies, does not seem to be dependent on the presence of specific immunoglobulin. This may explain the finding of specific IgG in an early stage after antigenic challenge. It seems likely that complement C3 fragments (likely C3d), bound to PPSs, enable PPS localization at B-cell and follicular dendritic cell surfaces by binding to CD21, the C3d receptor

Spleen autotransplantation provides restoration of functional splenic lymphoid compartments and improves the humoral immune response to pneumococcal polysaccharide vaccine

After splenectomy, patients have an increased risk of overwhelming post-splenectomy infection (OPSI) or sepsis involving encapsulated bacteria such as pneumococs. The value of spleen autotransplantation after splenectomy because of trauma has long been questioned. Much attention has been given to the restoration of mononuclear phagocyte system (MPS) function, which appeared to be similar to that of splenectomized individuals. The presence of specific anti-pneumococcal antibodies may enhance phagocytosis of opsonized bacteria by other parts of the MPS, as present in the liver. Therefore, in the present study we have evaluated the restoration of the humoral immune response after spleen autotransplantation, especially to pneumococcal capsular polysaccharides (PPS). Wistar rats were divided into three groups which were operated as follows: splenectomy, splenectomy followed by autotransplantation, and sham operation. After 12 weeks the rats were vaccinated with 23-valent pneumococcal vaccine. Blood samples were taken after 3 days, 3 and 6 weeks for anti-PPS IgM and IgG ELISA against types 3, 4, 6, 9, 14 and 23. In addition, immunohistological studies were performed on the autotransplants. Significant antibody titre rises were found in a main proportion of the autotransplanted rats, comparable to sham-operated rats. Splenectomized rats showed as well a significantly lower increase in immunoglobulin levels, as significant differences in the proportion of rats showing a minimum two-fold increase of antibody level, considered to represent an adequate response. The titres were highest 3 days after vaccination. Immunohistochemical studies demonstrated structurally functional autotransplants, including an intact marginal zone. Considering this significant anti- pneumococcal antibody response, spleen autotransplants can be expected to enable an improved humoral response to PPS, and to contribute to protection against OPSI after splenectomy