Human lymphocytes bear membrane receptors for C3b and C3d.

Human peripheral blood lymphocytes have membrane receptors for EAC43b (sheep erythrocytes sensitized with antibody and complement) and also for EAC43d, obtained by treating EAC43b with C3b inactivator. Human granulocytes bind only EAC43b, C3 fragments obtained by limited trypsin digestion of purified human C3 display both C3b and C3d sites, since they inhibit rosette formation of lymphocytes with EAC43b and EAC43d. These findings raise the possibility that C3b and C3d receptor sites may be selectively distributed among normal subpopulations of B lymphocytes as well as among leukemic leukocytes.

Complement-dependent release of immune complexes from the lymphocyte membrane.

Soluble antigen-antibody-complement complexes bound to mouse B lymphocytes are rapidly released from the cell membrane in the presence of normal serum from several mammalian species. The release is not the result of antigen-antibody dissociation or extensive degradation of the complexes. However, the released complexes have been altered because they will no longer bind to fresh lymphocytes.

Cell surface immunoglobulin. IV. Distribution among thymocytes, bone mrrow cells, and their derived populations.

Thymocytes, bone marrow cells, and their derived T and B cell populations were examined for the presence of Ig by the cell surface radioiodination technique. Both IgM and IgG were identified on bone marrow cells. Thymocytes and T cells had no detectable cell surface Ig.

Phagocytosis of immune complexes by macrophages. Different roles of the macrophage receptor sites for complement (C3) and for immunoglobulin (IgG).

Sheep red cells (E) sensitized with IgG antibody (EA) or with antibody and complement (EAC) interact in vitro with mouse peritoneal macrophage monolayers. The role of IgG and of C3 in the attachment and ingestion of the erythrocytes was examined by means of quantitative technique utilizing (51)Cr-labeled E. Controlled osmotic lysis permitted the separate measurement of the radioactivity associated with bound or with ingested E.

Theta-bearing and complement-receptor lymphocytes are distinct populations of cells.

In the mouse, most (or all) complement-receptor lymphocytes and theta-bearing lymphocytes are part of nonoverlapping populations of cells. This finding validates the use of these membrane markers to characterize populations of lymphocytes. In addition, it is probable that, although receptors for complement and membrane-bound immunoglobulins coexist on the same lymphoid cells, these markers are located at separate sites on the membrane.

Regulation of the immune response: suppressive and enhancing effects of passively administered antibody.

The ability of passively administered antibody to suppress the immune response against homologous antigenic determinants while concomitantly enhancing the response against other unrelated determinants of the same antigen molecule has been established in two distinct antigen-antibody systems: (a) guinea pig gamma(2)-immunoglobulin + passive anti-F(ab')(2) antibody, where suppression of anti-F(ab')(2) antibody synthesis is accompanied by enhancement of the anti-Fc response; and (b) human secretory IgA + passive anti-serum IgA antibody, where suppression of antibody production against the alpha and L chains accompanies augmentation of the response to the secretory component. The mechanisms of the suppressive and enhancing effects are probably unrelated for the following reasons: (a) Enhancement of the response to certain determinants may be obtained without discernible suppression of the response to the homologous determinants; and (b) the F(ab')(2) fragments of passive antibody can mediate immune suppression but were not observed to enhance the response against the unrelated determinants of the same antigen molecule. Also, the timing for achieving maximum suppression or enhancement of antibody formation is not the same; enhancement was obtained only at a later time.

Tissue localization of lymphocytes bearing a membrane receptor for antigen-antibody-complement complexes.

To determine the tissue localization of lymphocytes provisionally termed "complement-receptor lymphocytes," which are characterized by having a membrane receptor for antigen-antibody-complement complexes, we investigated the adherence of sensitized and nonsensitized sheep red cells to frozen sections of mouse lymphoid organs. Nonsensitized erythrocytes became bound exclusively to sinus-lining cells of spleen and lymph nodes, whereas erythrocytes sensitized with antibody and complement adhered to lymphocytes in the follicular areas and the marginal zone of the spleen and in the true cortex of lymph nodes. However, the doubly sensitized erythrocytes failed to bind to the "thymus-dependent" areas of peripheral lymphoid organs or to the thymus itself.

A population of lymphocytes bearing a membrane receptor for antigen-antibody-complement complexes. I. Separation and characterization.

A population of lymphoid cells from several animal species, including man, was identified through a membrane receptor which binds sheep red blood cells treated with antibody and complement. When cells from different lymphoid organs were incubated with EAC at 37 degrees C, only part of the lymphocytes (named CRL) bound EAC and formed rosettes, and this interaction was shown to be C3-dependent. Mouse lymphoid cells could be specifically depleted of CRL by allowing them first to interact with EAC and then submitting the mixture to ultracentrifugation in a gradient of BSA.