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Biomedical subjects

M Howard

Publications and source records attributed to M Howard.

At least 199 records · Page 11Linked to original sources
PubMed1983

Evidence for two distinct classes of murine B cell growth factors with activities in different functional assays.

Several previously described B cell growth factor (BCGF) activities from a number of mouse monoclonal T cell sources were compared in different functional assays. The results indicate that there are two distinct classes of BCGF defined by functional activity and source. BCGF I, whose prototype is (EL4)BCGF, synergized with anti-Ig in the proliferation of normal splenic B cells but had no activity when dextran sulfate (DXS), rather than anti-Ig, was used to costimulate the same source of B cells. BCGF I also failed to directly stimulate BCL1 tumor B cells. In contrast, BCGF II, whose prototype is (DL)BCGF, showed a reciprocal pattern of activity. BCGF II failed to synergize with anti-Ig-costimulated normal B cells to give good proliferative responses. Sources of BCGF II also directly stimulated (no anti-Ig or DXS added) B cells of the BCL1 tumor-carrying mice. These results suggest that the two BCGF may have activity on two subsets of B cells that respond differentially to induction with the two polyclonal B cell activators, anti-Ig and DXS. The possibilities that these different patterns of response occur in separate lineages of B cells and/or in B cells in different states of differentiation is discussed.

Animals↗
PubMed1983

Role of interleukin 1 in anti-immunoglobulin-induced B cell proliferation.

In this report we describe conditions for polyclonal activation of small numbers of highly purified mouse B lymphocytes. Three signals are required for induction of DNA synthesis by the particular subset of small B lymphocytes investigated: a signal delivered by antibodies specific for the IgM receptor expressed on the B cell membrane; a signal delivered by a T cell-derived factor (B cell growth factor [BCGF]); and a signal delivered by the macrophage-derived factor interleukin 1 (IL-1). The conclusion that IL-1 has B cell co-stimulator activity is based on the findings that highly purified preparations of mouse and human IL-1 have the capacity to cause proliferation in B cells treated with anti-IgM and BCGF. Such cultures show an absolute dependence on exogenously added IL-1 when 2-mercaptoethanol is omitted from the medium. BCGF and IL-1 each act in a non-antigen-specific, non-H-2-restricted, synergistic manner. Their requirement is not observed when B cells are cultured at high density, presumably reflecting accessory cell contamination and endogenous factor production under these conditions. The B cell activation induced by these three signals is restricted to proliferation without the production of antibody-forming cells.

Animals↗
PubMed1983

Resuscitation in hypovolemia and shock: a prospective study of hydroxyethyl starch and albumin.

In a prospective study comprising 50 patients, we evaluated the hemodynamic, pulmonary, renal and coagulation changes after resuscitation with 2 colloidal fluids, 6% hydroxyethyl starch (HES) and 5% albumin (ALB). Twenty-five patients studied in each group were well matched for age, clinical presentation, presence of shock and type of surgical procedures. A standard fluid challenge with 500 ml of either solution significantly (p less than 0.01) increased pulmonary artery wedge pressure (WP), mean arterial pressure (MAP) and left ventricular stroke work index (LVSWI) and decreased systemic vascular resistance index (SVRI). Increases in LVSWI of 43% to 68% over baseline in HES patients compared favorably to 15-22% increases in ALB patients. The cardiopulmonary variables at 12 and 24 h were comparable in both groups. Improvement in cardiac function was also reflected by better tissue perfusion as judged by reduction in arterial lactate from 2.9 to 1.5 mM/L (ALB) and 2.6 to 1.4 mM/L (HES). Increased O2 delivery and reduced O2 extraction without significant deterioration of PaO2 or alveolar-arterial O2 gradient were observed with stabilization of circulation. Clinical bleeding due to colloid resuscitation was not documented and renal function was not affected significantly by either fluid. It seems that HES may offer a cost-effective alternative to ALB for patients requiring colloid resuscitation.

Aged↗
PubMed1983

Regulation of B-cell growth and differentiation by soluble factors.

The B-lymphocyte family of cells presents one of the most remarkable opportunities for the detailed study of regulation of growth and differentiation. Some members of this cell population have the property that they may be stimulated by ligand-receptor interactions, together with the sequential action of a series of lymphokines, to progress from the resting state, through several rounds of proliferation, and then to differentiate to immunoglobulin secretion. Other cells in this group participate in cognate cellular interactions with helper T cells in which the recognition of both antigen and a class II MHC molecule on the B-cell surface is key to activation. The differentiation of these cells is also controlled by soluble products. We have reviewed our developing knowledge of the biochemistry and mode of action of the lymphokines that act upon B cells. These include distinct growth and differentiation factors. Among these are the BCGFs of mice and humans and the various TRFs, which include molecules often described as differentiation factors. The next several years should witness major progress in understanding the physicochemical properties of the B cell-specific factors, their time and nature of action, and the nature of their receptors. In addition, we can anticipate a major effort to understand the intracellular events that flow from the action of specific growth and differentiation factors that act upon B cells. Such information should lead to a new physiologically-based pharmacology for manipulation of antibody responses in human disease and in responses to vaccines. In addition, the fuller understanding of the nature and mode of action of the various growth and differentiation factors should make long-term growth of cloned B cells a procedure that can be routinely used in immunological laboratories for the precise study of the biology of responses by homogeneous populations of B lymphocytes.

Animals↗
PubMed1983

Biochemical and physicochemical characterization of mouse B cell growth factor: a lymphokine distinct from interleukin 2.

A subline of the C57BL/6 mouse EL-4 thymoma produces upon stimulation with phorbol myristate acetate (PMA) a B cell growth factor (BCGF) that co-stimulates anti-IgM-stimulated splenic B cells. The BCGF present in the EL-4 thymoma culture supernatants is shown to be distinct from IL 2 by a variety of chromatographic criteria. Untreated BCGF exhibits a heterogeneity of isoelectric points (pH 6.4 to 6.6, 7.4 to 7.6, 8.5 to 8.7) all of which are more alkaline than that of IL 2 (pl 3.5 to 4.8). Neuraminidase-treated BCGF exhibits a single major pl of 9.3 that is also distinct from similarly treated IL 2. Moreover, IL 2 and BCGF exhibit distinct monomeric m.w. by SDS gel electrophoresis under nonreducing conditions (IL 2 is 21,000; BCGF is 11,000 and 15,000). The biologic activity of IL 2 is sensitive to trypsin inactivation as is BCGF activity. Thus, BCGF and IL 2 appear to be biologically and biochemically distinct glycoproteins.

Animals↗
PubMed1983

T cell dependence and factor reconstitution of in vitro antibody responses to TNP-B. Abortus and TNP-Ficoll: restoration of depleted responses with chromatographed fractions of a T cell-derived factor.

In vitro anti-trinitrophenyl (TNP) antibody responses to TNP conjugates of killed Brucella abortus organisms (TNP-BA), an antigen previously designated as a type 1 thymus-independent (TI-1) antigen, are markedly diminished after vigorous depletion of T cells, as are the responses to the type 2 TI (TI-2) antigen, TNP-Ficoll. We, therefore, propose that these antigens be redesignated as type 1 and type 2, respectively, to reflect their T cell dependence but to differentiate them from classical T cell-dependent (TD) antigens. T cell-depleted responses to type 1 and type 2 antigens can be restored by the addition of a) EL4 supernatant, b) phenyl-sepharose-purified fractions of EL4 supernatant that are rich in interleukin 2(IL2), and c) pl 4.5-5.5 isoelectric focused (IEF) fractions of EL4 supernatant which are also rich in IL2 activity. Removal of IL2 activity from EL4 supernatant by absorption on IL2-dependent T cells substantially reduced its restorative ability. Whether the active principle in EL4 supernatant activity responsible for restoring responses to type 1 and type 2 antigens is IL2, and whether it acts directly on B cells or by acting on contaminating T cells, is unresolved.

Animals↗
PubMed1983

Soluble factors involved in B cell differentiation: identification of two distinct T cell-replacing factors (TRF).

Highly purified B lymphocytes cultured with affinity-purified goat anti-mouse IgM antibodies and B cell growth factor (BCGF) proliferate but fail to differentiate into immunoglobulin-synthesizing cells during 4-day cultures. Induction of immunoglobulin (Ig) synthesis depends on the presence of two additional T cell-derived factors (T cell-replacing factors [TRF]). One TRF, designated B15 1K 12-TRF, is found in the supernatant of B15 1K 12 T hybridoma cells. It is required relatively early in these cultures and appears to cause an increase in cell yield as well as Ig synthesis. The second factor, designated EL-TRF, is found in PMA-induced EL-4 supernatant. It appears to be different from both BCGF and IL 2 in that it can be separated from the former by isoelectric focusing and from the latter by phenyl-Sepharose chromatography. EL-TRF is still active if added on the last day of a 4-day culture. A model for the action of anti-IgM and these three T cell-derived factors in B cell activation and differentiation is proposed.

Animals↗
PubMed1982

Identification of a T cell-derived b cell growth factor distinct from interleukin 2.

We report here a factor (B cell growth factor) found in induced supernatants of the mouse thymoma EL4 that co-stimulates with anti-IgM antibodies in short-term cultures of purified B lymphocytes to induce polyclonal B cell proliferation but not antibody-forming cell production. The factor is not mitogenic for resting B cells and interacts with anti-IgM-activated B cells in a non-H-2-restricted manner. Absorption studies and molecular weight analysis reveal the factor is distinct from interleukin 2. This factor synergises with antigen, interleukin 2, and an interleukin 2-free, B cell growth factor-free T cell supernatant that contains T cell-replacing factor to produce erythrocyte-specific plaque-forming cells in cultures of highly purified B cells.

Animals↗
PubMed1982

Cell cloning as a tool to analyze the immune response.

Long-term lines of cloned, immunocompetent, nontransformed lymphocytes have the potential to allow the direct examination of many of the key aspects of lymphocyte activation and regulation. We describe here techniques for the long-term propagation of nontransformed human and mouse B-lymphocytes. These lines have the shared characteristics in that they bear membrane Ig, that their growth depends on the presence of appropriate growth factors, and that, when properly stimulated, they secrete Ig. We found that the human lines are negative for Epstein-Barr nuclear antigen and that they can be cloned by limiting dilution. A long-term line of human B-lymphocytes we prepared by limiting dilution cloning contained only lambda light chain-bearing cells.

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