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F W Shen

Publications and source records attributed to F W Shen.

At least 55 records · Page 3Linked to original sources
PubMed1984

Induction of T-cell differentiation.

T cell development can be viewed as precursor cells migrating from yolk-sac and liver in the embryo, and bone marrow and spleen in the adult to the thymic cortex as functionally immature T-cells, and to the medulla where they acquire immunological function, and finally joining the pool of T-cells in the blood lymphoid system and spleen. Several cell surface markers were used to study these processes, such as TL, Ly-1, Ly-2/3, Qa-1, and I-J. Using these cell surface markers combined with biologically active reagents in functional tests in vitro, several conclusions can be drawn to illustrate these differentiation steps. 1) T cell precursors are precommitted and can be separated from other hematopoietic stem cells. 2) During induction of prothymocytes several new unlinked gene products are expressed. 3) Thymopoietin is a physiological inducer. 4) This induction to express new surface markers requires transcription and translation but is independent of DNA synthesis, at least according to the action of metabolic inhibitors. 5) Surface phenotypes and function of cells are coordinately programmed. 6) Most Ly1 and Ly23 cells, if not all, are derived from Ly123 precursor cells. 7) Acquisition of new surface phenotype precedes new functional expression, supporting the hypothesis that the differentiation process consists in pre-mitotic expression of a gene set for phenotype, and postmitotic expression of a set for function. 8) The differentiation steps require cell-cell interaction, either by direct contact or by soluble factors within the same T-cell linkage.

Animals↗
PubMed1983

On the function of Ly-5 in the regulation of antigen-driven B cell differentiation. Comparison and contrast with Lyb-2.

Generation of anti-sheep erythrocyte plaque-forming cells (PFC) is greatly reduced in the presence of monoclonal Ly-5 alloantibody. Although Ly-5 is expressed in one of its molecular forms on T cells and macrophages (M phi ) involved in this response, the only demonstrated action of Ly-5 antibody was on B cells. Evidence from elimination of Lyt-2+ cells, and from the responses of serial proportions of Ly-5.1 and Ly-5.2 cells and of Ly-5 heterozygous cells, signifies that PFC reduction cannot be ascribed to any known mechanism of suppression or to a direct suppressive action of Ly-5 antibody on B cells. A critical distinction of Ly-5 from Lyb-2 is that Ly-5 antibody reduces PFC generation to trinitrophenylated Ficoll, a thymus-independent type 2 antigen requiring T cells and M phi for maximal PFC generation in vitro. A second distinction is that PFC reduction by Ly-5 antibody is strictly tied to the time of operation of M phi factor, whereas PFC reduction by Lyb-2 antibody relates to the time of B cell triggering by antigen. Accordingly, M phi factor competitively and quantitatively inhibits the action of Ly-5 antibody in reducing PFC generation. It is likely that the Ly-5 system is concerned in the reception or handling of M phi message by B cells.

Animals↗
PubMed1982

Evidence that Lyb-2 is critical to specific activation of B cells before they become responsive to T cell and other signals.

The generation of plaque-forming cells (PFC) to T-dependent antigen, but not to T-independent antigen, is reduced in vitro by Lyb-2 antibody. Monoclonal Lyb-2 antibody, added to Mishell-Dutton cultures within the first 2 d, but not later, greatly reduces the generation of alpha-sheep erythrocyte (SRBC) PFC from T-depleted spleen cells whether help is provided in the form of intact T cells or as soluble factors contained in mixed lymphocyte culture (MLC) supernatants. Generation of alpha-SRBC PFC from purified B cells, assisted by soluble factors in MLC and macrophage (P388D.1 cell) supernatants, is similarly reduced by Lyb-2 antibody. The initial 2-d period, during which cultures are diminishingly sensitive to reduction of PFC generation by Lyb-2 antibody, is not affected by the time at which such soluble factors are added. Thus, Lyb-2 cell surface molecules evidently do not function as receptors for these differentiative signals. Reduction of PFC generation by Lyb-2 antibody is antigen dependent in the sense that reduction of the PFC response to one antigen (SRBC) does not affect subsequent generation of PFC to a second antigen (horse erythrocytes) from the same cell population. These findings accord with the view that the Lyb-2 molecule participates in a B cell differentiative phase, probably proliferative, which begins with binding of antigen and precedes the phase in which B cells become fully receptive to signals from T and other cells.

Animals↗
PubMed1982

Two Ly-2 T helper cell subsets distinguished by Qa-1 phenotype. The priming environment determines whether one or both subsets will be generated.

The Qa-1 cell surface phenotype reportedly distinguishes two Ly-1 T cell subsets conjointly required for T helper effector activity. Ly-1 cells, obtained from several different priming regimens, were negatively selected with anti-Qa-1 plus complement and compared with unselected Ly-1 cells for helper cell activity. Priming isolated T cells on antigen-pulsed macrophages in the absence of B cells favors the generation of the Ly-1:Qa1- subset, which is capable of efficient helper activity in the absence of the Ly-1:Qa-1+ subset. Priming T cells in an environment containing B cells generates both Ly-1:Qa-1- helper effector cells and Ly-1:Qa-1+ cells which contribute to the helper effect. Whether Ly-1:Qa-1+ cells are capable of independent helper activity cannot be determined, and, as such, Ly-1:Qa-1+ cells are more appropriately termed "help associated" rather than "helper effector." Our results assign a membrane phenotype, Qa-1, which distinguishes an Ly-1 help-associated B cell requiring subset in our system and may prove to be a general marker in a number of systems of Ly-1 inducer cell subsets which functionally require or recognize B cells or their products.

Animals↗
PubMed1982

Further polymorphism of the Tla locus defined by monoclonal TL antibodies.

Six new monoclonal TL antibodies are described. At least one new TL antigen is defined (TL.7), and at least one more Tla allele, bringing the total number of known Tla alleles to six. Five of the monoclonal antibodies, and probably all six, identify distinct TL antigenic specificities. Four of these antigens conform in strain distribution and expression on leukemia cells to antigens defined by conventional antisera. The data contain a hint that monoclonal TL antibodies like TL.m6 may serve to identify a region of the Tla gene, which determines whether or not prothymocytes will respond to physiological induction by expressing TL, and thus may provide a means to study the regulatory mechanism that determines whether mouse strains are phenotypically TL+ or TL-.

Alleles↗
PubMed1982

A system of alloantigens that selectively identifies lymph-node lymphocytes.

The antiserum (BALB.I-H-2j x SWR/J)F1 anti-I.29 ascites cells, in reaction with B6 lymph-node cells (LNC) in the cytotoxicity assay, defines an alloantigen system called Lna-1 (lymph-node alloantigen-l) which in normal, untreated mice is expressed on the cells of lymph nodes but not of other lymphoid organs. The T- and B-cell populations of lymph nodes evidently include Lna-1+ subpopulations representing 30-40 percent of the total population The Lna-+ phenotype could be induced on cells of thymus and spleen but not of bone marrow. Congenitally asplenic +/Dh mice have no Lna-1+ cells in their lymph nodes, but their LNC can be induced to express Lna-1; this suggests that the spleen is normally required for the differentiation of Lna-1+ cells from Lna-1- precursors. It is not yet known whether thymus is also required for the expression of Lna-1 in lymph nodes. It remains to be seen whether the existence of the Lna-1+ B-cell subpopulation of lymph nodes depends on Lna-1+ T cells, and whether the Lna-1+ phenotype of B cells may be acquired rather than intrinsic. One hypothesis which is the basis of further study is that there is a T-cell pathway in which noninducible bone-marrow cells become Lna-1-inducible in the thymus, then travel to the spleen, where they are induced to become Lna-1+, after which they reside in lymph nodes.

Animals↗
PubMed1982

Structure of the murine plasma cell alloantigen PC-1: comparison with the receptor for transferrin.

The plasma cell alloantigen PC-1 was isolated from C1.18 myeloma cells by immunoprecipitation and was analyzed by polyacrylamide gel electrophoresis. It was found to consist of two similar or identical disulfide-bonded polypeptide chains, each of Mr 115,000. The mobility of PC-1 in nonequilibrium pH gradient electrophoresis was similar to that of bovine serum albumin (pI 4.9). The PC-1 antigen is therefore similar to the transferrin receptor in Mr, charge, subunit composition, disulfide bonding, and developmental regulation. Similarities can also be detected by peptide mapping with subtilisin, but not with staphylococcal V8 protease. It is suggested that the PC-1 protein and the transferrin receptor may have had a common evolutionary origin, and may have similar functions.

Animals↗
PubMed1981

T cell development. Precursors and inducer requirements of helper effector and feedback suppression inducer cell sets.

The surface phenotypes and differentiative history of specific helper-effector (HE) and specific feedback suppression-inducer (FBSI) cell sets were further defined in reference to the Qa-1 and I-J marker systems by culture of selected sets of cortisone-resistant nylon-purified thymocytes with antigen on primed macrophages. The generation of Ly-1:HE and Ly-1:FBSI cell sets required, in each case, two initiating sets: a precursor set and a differentiation-inducing set. Precursor sets were distinguished from inducer sets by genetic markers. Accordingly, HE cells, phenotype Ly-1:Qa-1-:I-J-, differentiated from Ly-123:Qa-1- cells in the presence of Ly-1:Qa-1+:I-J+ inducer cells; and FBSI cells, phenotype Ly-1:Qa-1+:I-J+, differentiated from Ly-123:Qa-1- in the presence of Ly-1:Qa-1+:I-J+ inducer cells. The Ly-123:Qa-1-precursors of HE and FBSI cells have been distinguished from one another previously but there is as yet no evidence whether differentiation of these precursor sets requires the same or different Ly-1:Qa-1+:I-J+ inducer sets.

Animals↗
PubMed1981

Contrasuppression. A novel immunoregulatory activity.

We have described an interaction between two T cells subsets that results in interference with the expression of Ly-1-, 2+ (Ly-2) T cell-mediated suppression. We refer to this novel immunoregulatory activity as contrasuppression. The T cell responsible for the induction of contrasuppression (inducer cell) expresses the phenotype Ly-1-, 2+;I-J+;Qa-1+. This phenotype distinguishes it from the suppressor effector cells which we find to be I-J-2.3. An I-J+ soluble mediator from the contrasuppressor inducer cell acts on another cell (acceptor cell) that expresses the phenotype Ly-1+, 2+; I-J+; Qa-1+. This phenotype distinguishes it from T helper cells. Both the inducer cell (or its biologically active mediator) and its acceptor cell are required for the expression of contrasuppression. Because contrasuppressor cells can block the suppressive activity of cell-free mediators released by Ly-2 suppressor T cells, the mechanism of contrasuppression is either separated from or in addition to the inactivation of suppressor cells themselves. The potential importance of contrasuppressor activity in the regulation of suppressor T cell activity in allowing immunologic memory to be expressed and in permitting microenvironmental immune regulation is discussed.

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