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H Yakura

Publications and source records attributed to H Yakura.

54 records · Page 3Linked to original sources
PubMed1988

[Induction of thymocyte proliferation with B cell stimulatory factor-1].

Murine B cell stimulatory factor (BSF)-1 or interleukin 4 has been shown to regulate various aspects of B cell activation and differentiation. More recently it has been shown that this lymphokine is also involved in the regulation of T cell and mast cell proliferation. In this study we purified BSF-1 activity from supernatants of T cell hybridoma FS6-14. 13 and tested its activity on a variety of in vitro assays. It was found that the purified BSF-1 material has various activities previously ascribed to BSF-1, and interestingly enough it also induces strong proliferation of thymocytes in collaboration with phytohemagglutinin. These results strongly suggest that BSF-1 plays a regulatory role in thymocyte differentiation and further support the notion that lymphokines generally have a broad spectrum of activity.

Animals↗
PubMed1986

A role for Lyb-2 in B cell activation mediated by a B cell stimulatory factor.

The Lyb-2 system of the mouse is involved in regulation of a proliferative step in the differentiation of B cells responding to T-dependent antigen. The present study concerns the role of Lyb-2 in an early phase of B cell activation with respect to B cell receptor functions for activation factors. It is shown that interaction of monoclonal anti (alpha)-Lyb-2 antibody with Lyb-2 on the B cell surface induces B cell proliferation by synergistic action with B cell growth factor II-containing factor or interleukin 1. In contrast, alpha-Lyb-2 antibody could not synergize with the Con A-induced culture supernatant of T cell hybridoma FS6-14.13 (FS6) containing B cell stimulatory factor-1 (BSF-1; formerly called BCGF I), and the effect of combining the two was only additive on B cell proliferation. Absorption studies showed that BSF-1 in FS6 could be absorbed by unstimulated B cells, about 95% of which were at Go phase of the cell cycle, but not by thymocytes, and more importantly that alpha-Lyb-2 antibody blocked the absorption in an Lyb-2-specific manner, possibly by competing with BSF-1. It is thus likely that alpha-Lyb-2 antibody may interact with a BSF-1 receptor on B cells or a molecule closely associated with it. Interestingly, alpha-Lyb-2 antibody mimicked the action of BSF-1 in a costimulator assay with affinity-purified goat alpha-mouse IgM antibody, but could not replace all the activities ascribed to BSF-1. Possible mechanisms involved are discussed.

Animals↗
PubMed1986

Selective inhibition of lipopolysaccharide-induced polyclonal IgG response by monoclonal Ly-5 antibody.

We have identified two important molecules involved in the regulation of B cell differentiation, namely Lyb-2 and Ly-5. To gain further insight into the function of these two molecules, we examined the effect of monoclonal Lyb-2 and Ly-5 antibodies on lipopolysaccharide (LPS)-induced B cell growth and maturation. We found that Lyb-2 antibody does not have any effect on LPS-induced proliferation and on polyclonal IgM or total IgG responses. On the other hand, although Ly-5 antibody did not affect proliferation and polyclonal IgM responses, it strongly inhibited polyclonal IgG responses, presumably by direct action on B cells. This inhibition was not caused by direct suppressive effect of Ly-5 antibody or Fc receptor-mediated negative signaling. To exert maximal inhibitory effect, Ly-5 antibody had to be added to the culture during the initial 48 hr. However, the presence of Ly-5 antibody during the first 2 days did not cause a significant inhibition. It is thus likely that Ly-5 plays a critical role in the regulation of LPS-induced B cell maturation into IgG-secreting cells at a phase starting within 48 hr after LPS stimulation and continuing thereafter.

Animals↗
PubMed1986

[Treatment with K-18 (IgG-melphalan) in recurrent cases of hematopoietic malignancies].

K 18, an IgG-Melphalan conjugate was administered to 30 patients, who had recurrent hematopoietic malignancy. Ten out of the 30 patients received single doses of 1 to 20 enteric tablets containing 10 mg of K 18, as a phase I study. No side effects were observed. K 18 was administered every day to the remaining 20 patients in order to evaluate the side effects and therapeutic effects, as a phase II study. One patient attained partial remission. Although no remission effect was obtained in 14 of the 20 patients, antitumor effects such as a decrease in leukemia cells, were observed in 4 of 20 patients. As to side effects, neither recurrence of tumor nor cumulative toxicity were shown in one patient with NHL who received only K 18 for 14 months as maintenance therapy. Evaluation of antitumor effect was difficult in the case of the remaining 4 patients. In the 20 cases who entered the phase II study, a decrease in neutrophils was observed in 2 patients, a slight decrease in platelets in 3 patients and increased transaminase activity in one patient as side effects of K 18. In brief, compared with Melphalan, K 18 has between 1.3 and 2 times a more potent therapeutic effect, with extremely low side effects.

Administration, Oral↗
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↗
PubMed1981

Lyb-2 system of mouse B cells. Evidence for a role in the generation of antibody-forming cells.

The Lyb-2 cell-surface alloantigens of the mouse are selectively and perhaps exclusively expressed in the B lymphocyte lineage, but not on antibody- forming cells. Thus if the Lyb-2 molecule is concerned in specific B cell function, it must participate in the generative phase of the antibody response. Accordingly, monoclonal Lyb-2 antibody was found to depress the plaque- forming cell (PFC) response to sheep erythrocytes in 5-d Mishell-Dutton assays when added within the first 3 d of culture, but not later. The rate of PFC generation was not affected, signifying an absolute reduction in the number of PFC generated. Because reduction of PFC counts by Lyb-2 antibody was not affected by exclusion of Lyt-2(+) T cells, it is unlikely that the reduction depends on augmented suppression by T cells. Augmented B cell- mediated suppression is also unlikely, because the PFC response of serial combinations of congenic Lyb-2.1 and Lyb-2.2 cells, in the presence of monoclonal Lyb-2.1 antibody, was reduced only in direct proportion to the number of Lyb-2.1 cells present. The PFC response of Lyb-2.1/Lyb-2.2 heterozygous cells was not reduced by Lyb-2.1 antibody, presumably because generation of PFC is impeded only if most Lyb-2 sites are blocked. Further evidence that the molecule identified by Lyb-2 plays a critical role in the generation of antibody-forming cells (AFC) in response to T-dependent antigen comes from the finding that Lyb-2 antibody does not reduce the PFC response to the T-independent antigens trinitrophenylated (TNP) Brucella abortus and TNP-FicolI, although elimination of Lyb-2(+) cells from the starting population by Lyb-2 antibody and complement reduces the PFC response to T- dependent and T-independent antigens alike.

Animals↗
PubMed1977

An HLA-D specificity found in the Japanese population.

A new HLA-D specificity was found in the Japanese population in two different laboratories. Japanese cell YT, found at Stanford, California, was A9,BW22J,CW1 and cell Wa, found at Sapporo, Japan, was A9,BW22J homozygous. They were shown to be HLA-D identical to the homozygous Japanese cell AH which submitted to the VIth International Histocompatibility Testing Workshop (Workshop number 2-001). This specificity was common in the Japanese (gf = 0.089) but completely absent from 62 Caucasians tested. Strong association of this specificity with HLA-BW22J was demonstrated.

California↗
PubMed1976

Inheritance of asthma in families and its linkage to HLA haplotypes.

Four families in which asthma occurred in more than three members, and in which there were at least three children, were studied in terms of clinical symptoms, serum IgE levels determined by RIST and RAST, and HLA haplotypes. No association between clinical asthma and serum IgE level was found, but a close association between asthma and a particular HLA haplotype in a family was demonstrated. It was therefore postulated that a disease susceptibility gene closely linked to an HLA gene complex may play a role in the development of asthma.

Asthma↗
PubMed1976

HLA-D antigen of Japanese origin (LD-Wa) and its association with Vogt-Koyanagi-Harada syndrome.

One homozygous cell "Wa" for HLA-D alleles, associated with HLA-Bw22J (Japanese specific variant of HLA-Bw22), was found in a Japanese family. The HLA-D antigenic specificity defined by this cell has been tentatively named LD-Wa. Phenotype frequency of LD-Wa in the Japanese population was 0.16 (13/81). HLA-D typing for LD-Wa was performed in patients with the Vogt-Koyanagi-Harada syndrome (Harada's disease) with which Bw22J is strongly associated (15/35, 42.9%; corrected P less than 0.02). LD-Wa was presented in 22 of 33 patients (33.7%; P less than 0.0000003). The association of LD-Wa with Harada's disease was stronger than that of Bw22J, and this implies that there might be one of the disease susceptibility gene loci affecting the development of this disease more closely linked to an HLA-D gene locus than the HLA-B locus.

Epitopes↗