A BS T R A C T Sheep red blood cells can surround, in vitro, some human peripheral blood lymphocytes in a formation called a rosette. The number of rosetteforming cells (RFC) in 50 normal persons had a wide range (4-40%). The organs of 13 human fetuses (11-19 wk conceptional age) were examined for the presence of RFC. The thymus possessed the highest percentage of RFC, the maximum being 65% of total thymocytes in two 1516 wk fetal specimens. Blood RFC were always present and their number slightly increased in the oldest fetuses. The bone-marrow showed 0-8% in the six fetuses studied. RFC were found in the spleen around the 13th wk and in the liver around the 17th wk of gestation. These observations lead to the hypothesis that human blood RFC may be chiefly thymic derived. Studies of patients with immunological disorders support this hypothesis: one patient with Nezelof syndrome had no blood RFC and four patients with Wiskott-Aldrich syndrome had a low number of blood RFC (1 and 1.5%). Patients with acquired hypogammaglobulinemia showed a normal percentage of RFC. With the fetal thymocytes, the percentage of inhibition with anti-i, serum increased with the fetal age to become complete in the oldest fetuses studied. Incubation of the oldest fetal thymocytes or the blood lymphocytes with anti-e serum or anti-ja serulmi completely inhibited the rosette formation. These results suggest that u-chain determinants are presenit on human fetal thymocytes and blood RFC. The significance of the presence of y-chain determinants on these cells is uniclear.

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The Human Rosette-Forming Cell as a Marker of a Population of Thymus-Derived Cells

Publisher Summary This chapter describes membrane immunoglobulins and antigen receptors on B and T lymphocytes. There are several qualitative and quantitative distinctions between T-cell and B-cell M-Ig that may explain many of the apparent differences in reactivity of these cells without requiring the existence of a different set of V genes or non-Ig receptors in T cells. Both T and B cells derive from hematopoietic, precursor, stem cells by antigen-independent differentiation. This involves the activation of L-chain and p-type H-chain genes in both cell types. The T-cell and B-cell M-Ig differ primarily in density per cell and possibly in relative exposure on the cell surface with much of the H-chain Fc region inaccessible on T cells. Moreover, the antigen-recognition receptor of both T and B cells involves their M-Ig. On B cells, the receptor is solely the M-Ig, whereas on T cells it is suggested that the specificity of recognition controlled primarily by the M-Ig and binding of antigen to the cell can solely be by the M-Ig receptor. Finally, the activation of the T cell requires an additional interaction of the antigen with another ceIl surface structure that is coded for by a polymorphic H-2 linked gene.

Membrane immunoglobulins and antigen receptors on B and T lymphocytes.

Peripheral lymphocytes from 25 patients with chronic lymphocytic leukemia (CLL) and three with chronic lymphosarcoma-cell leukemia, and lymph-node cells from three of four with lymphocytic lymphoma bore on their cell surface IgM, which was readily demonstrated with fluorescein-conjugated antiserums. The lymphosarcoma cell differed from the cell of CLL in possessing much more surface immunoglobulin. Light-chain analysis of the surface IgM showed that cells bore either kappa or lambda determinants, but not both, indicating the clonal nature of these neoplasms. The serum of four leukemic patients was also found to contain small amounts of IgM M-components. Since the B lymphocyte (bone-marrow-derived) of laboratory animals bears large amounts of surface immunoglobulin and the T lymphocyte (thymus processed) does not, the findings favor the B-cell origin of these leukemic cells. A less likely possibility is that the CLL lymphocyte is a derepressed T cell.

Immunoglobulins on the surface of neoplastic lymphocytes.

Publisher Summary This chapter focusses on the study of cell-mediated immunity in vitro, principally in terms of explaining the effector process of the response. To organize the observations in many species and systems, four general assumptions has been made. First, the diversity of information for cell-mediated immunity is carried by lymphocytes, and is of the same order of magnitude and specificity as for circulating antibodies. Second, all cell-mediated immune reactions have a common basis, including the tuberculin-type reaction, contact hypersensitivity, cellular resistance to infection, allograft rejection, and tumor immunity. Third, the increase in responsiveness after a process of sensitization or immunization is consistent with a clonal selection by the antigen of reactive cells. Information for cell-mediated immunity is carried by thymus-dependent lymphocytes, but whether their specificity is generated by genes informational molecules from other cells or antigen itself remains unclear. Fourth, the mechanisms of effector reactions mediated by delayed-type hypersensitivity and humoral antibody are fundamentally different. Explicit discrimination between these two mechanisms must be made wherever possible, not only in vivo but in vitro as well.

In Vitro Approaches to the Mechanism of Cell-Mediated Immune Reactions

Peripheral blood lymphocytes from normal subjects as well as patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and active tuberculosis were studied for the relative distribution of bone marrow-derived lymphocytes (B-cells) and thymic-derived T-cells. B-cells were identified by direct immunofluorescence of surface Ig markers; T-cells were studied using rabbit antisera to pooled human fetal thymocytes absorbed with chronic lymphatic leukemia lymphocytes as a source of B-cells. In normal subjects, the sum of percentages of peripheral blood lymphocytes staining for surface Ig (B-cells) plus the percentage of cells staining with the absorbed antithymocyte antiserum closely approximated 100%. The mean value for percent B-cells among 51 normals tested was 22.9%+/-7.1; mean T-cells value was 75.3+/-13.95%. T-cell-specific antiserum stained 18% of normal human bone marrow lymphocytes, 42.5% of lymphocytes from normal spleens, and 98% of cells obtained from thoracic duct drainage of patients with RA. Specificity of antihuman thymocyte antiserum appeared to depend on the use of living cells. When patients with RA were examined, a wide range (14-98%) of peripheral blood T-cell values was found. Values for low percentages of peripheral blood T-cells appeared to correlate to some extent with severe clinical disease. In 11 of 36 RA patients, the sum of identifiable B- plus T-cells accounted for only 34-55% of peripheral blood lymphocytes. The identity of the remaining "null" cells could not be identified.3 of 24 SLE patients studied showed low percentages of peripheral blood T-cells, but no correlation could be drawn between T- to B-cell ratios and clinical disease activity. Among 21 patients with active tuberculosis, one had a low value for identifiable T-cells. No significant differences from normals in range or proportion of B-cells was identified in patients with active tuberculous infection.

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Studies of T- and B-Lymphocytes in Patients with Connective Tissue Diseases

Surface immunoglobulin-moieties on lymphoid cells.

Immunoglobulin moieties on the surface of Burkitt lymphoma and chronic lymphocytic leukaemia cells were demonstrated by immunofluorescence, agglutination and the cytotoxic effect of anti IgM and anti x serum. Using purified IgM from human serum as a reference the amount of immunoglobulin on these cells could be quantitated by their efficiency in absorbing anti-IgM and anti-x serum. The residual activity of the sera was tested in three different systems. The amount of IgM on cells of a culture line derived from a Burkitt lymphoma and on cells from a patient with chronic lymphocytic leukaemia was about 25 μg/109 cells. Cells from further cases of chronic lymphocytic leukaemia showed weak reactivity with fluorescein-labelled anti-IgM serum and carried lower but detectable amounts of IgM. Cells with accumulations of IgM structures on the cell membrane were found in normal lymphoid populations obtained from human foetus and adult bone marrow by immunofluorescence. Similar cells were also seen in mouse and rabbit lymphoid cell populations.

Eva Klein

Papers

Surface immunoglobulin-moieties on lymphoid cells.

Surface immunoglobulin-moieties on lymphoid cells.

Growth of small compatible tumor implants in presence of admixed radiation-killed or incompatible tumor cells.