Gary Birnbaum

Determination of antibody avidity at the cellular level by the plaque inhibition technique: effect of valence of the inhibitor.

Inhibition of plaque formation by multivalent and univalent ligands was compared as an assay of avidity of antibody produced by PFC. Multivalent ligands are much more effective as inhibitors and their use tends to impart an appearance of lack of heterogeneity and high avidity to the PFC populations being studied. It is thus probably generally advisable to employ univalent ligands in such studies.

Studies on brain-thymus cross-reactive antigens

An antigen(s) shared by mouse brain and thymocytes was studied with the use of a rabbit anti-mouse brain antiserum (RAMB). Full complements of brain-thymus antigen were found on the brains of several mouse strains, including athymic mice, regardless of their theta antigen genotype. Brain-thymus antigen(s) was absent in newborn mouse brains and gradually reached adult levels two weeks after birth. Treatment of mouse brain with trypsin neither decreased nor increased the amount of the brain-thymus antigen available for absorption of RAMB. Mouse brain-thymus antigens were present on rat thymocytes, but not rat brain. The concentrations of brain-thymus antigens were 3- to 4-fold higher in gray matter than white matter. Cross-absorption studies with RAMB and anti-theta antiserum suggest that theta antigen and brain-thymus antigen are two distinct substances, both antigenically and in their anatomical localization on brain cells.

Lymphocyte Transformation Induced by Autologous Cells: Stimulation by Cultured Lymphoblast Lines

The ability of cultured lymphoblasts to stimulate autologous lymphocyte transformation in one-way mixed leukocyte culture has been studied. Intact, cultured lymphoblasts required physical contact with responding lymphocytes to induce transformation. In quantitative terms, lymphocytes incorporate as much thymidine when mixed with irradiated cultured lymphoblasts as they do in response to phytohemagglutinin. The stimulation of lymphocyte transformation by allogeneic cultured lymphoblasts did not parallel the stimulation of lymphocyte transformation by leukocytes from the donor of the lymphoblast culture. The stimulatory determinants on the cultured lymphoblast are unaffected by neuraminidase but destroyed by trypsin. The trypsin-treated cultured lymphoblasts regain their capacity to stimulate autologous lymphocyte transformation within 48 hr in culture. Cultured lymphoblasts possess concanavalin A binding sites. Concanavalin A inhibits the capacity of cultured lymphoblasts to stimulate autologous lymphocyte transformation. The relevance of these findings to EB virus infection of cultured lymphoblasts and to immune surveillance is discussed.

Human suppressor lymphocytes: I. Induction and characterization

Abstract Human peripheral blood lymphocytes were induced to become suppressor cells by exposure to Concanavalin A or Phytohemagglutinin. These cells were able to suppress the cytotoxic responses but not the proliferative responses of alloantigen activated human lymphocytes. Suppressor cells were non-specific in their activity, suppressing both allogeneic and syngeneic responders. They were labile in short-term tissue culture and required a proliferative phase for full induction of suppressor activity. Removal of macrophages prior to mitogen exposure resulted in a small loss of suppressor activity. Suppression was not the result of too much help since enhancement could not be demonstrated upon the addition of small numbers of suppressor cells to MLC.

Autologous and allogeneic stimulation of peripheral human leukocytes

Abstract Lymphoid cell lines have been established from four normal donors. When irradiated cells from these lines were mixed with either allogeneic or autologous peripheral leukocytes, marked increases in thymidine incorporation by the peripheral leukocytes were noted. This marked stimulatory capacity was not the result of the presence of soluble mitogens.

Numbers of rosette forming cells in human peripheral blood

Abstract Thymus-derived (T-cell) and “bursal” derived (B-cell) lymphocytes in human peripheral blood were quantitated by assaying percentages of cells forming erythrocyte rosettes. T-cell rosettes were formed with neuraminidase treated sheep erythrocytes. B-cell rosettes were formed with complement coated sheep erythrocytes. Large differences in the percentages of T-rosette forming cells were noted depending on the method used to assay these cells. When rosette forming cells (RFC) and non-RFC were counted concurrently the percentage of T-cell rosettes were 53–75% whereas methods involving the separate counting of RFC and total cells gave T-cell RFC percentages of 23–40%. These differences were due to the “co-rosetting” of non-RFC into the T-cell rosette clusters. This occurred because of the gentleness required to resuspend the fragile T-cell rosettes. “Co-rosetting” was demonstrated by forming stable complement receptor rosettes with complement-coated human erythrocytes and resuspending them either gently or vigorously. Significantly higher percentages of rosettes were noted with gentle cell suspension than with vigorous resuspension. The percentages of rosette forming T-cells in human peripheral blood are therefore lower than previously estimated.

ANTIBODY-MEDIATED TOLERANCE

Publisher Summary This chapter provides an overview of antibody-mediated tolerance. Immunological tolerance, if defined in operational terms, refers to a specific depression of antibody synthesis as a result of previous exposure to antigen. A tolerant state can exist as a result of specific inhibition of either or both T lymphocyte or B lymphocyte function. Passively administered antibody will specifically depress the immune response to concomitantly injected antigen. The chapter presents the characterization of a state of specific immunological tolerance that was induced in adult mice by a single intravenous injection of a soluble, although presumably somewhat aggregated antigen. This tolerance state is mediated by the production of relatively high affinity serum antibody as a result of the tolerance-inducing injection of antigen. Tolerance in the experimental model presented in the chapter appears to be the consequence of a normal immune response to an immunogenic antigen.