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Biomedical subjects

I Scher

Publications and source records attributed to I Scher.

At least 37 records · Page 2Linked to original sources
PubMed1983

Leukapheresis in rheumatoid arthritis. Association of clinical improvement with reversal of anergy.

In order to study the clinical and immunologic effects of a brief course of leukapheresis, 14 patients with clinically similar rheumatoid arthritis were segregated into 2 subgroups. Group A (7 patients) had subnormal lymphocyte tritiated thymidine incorporation to soluble antigens. After a brief course of leukapheresis, 6 of these 7 patients demonstrated substantial clinical improvement associated with significantly enhanced lymphocyte tritiated thymidine incorporation to soluble antigens. In contrast, none of the 7 patients in group B (normal immune functions) demonstrated similar changes in articular indices or lymphocyte proliferation. Thus, clinical improvement induced in a subset of rheumatoid arthritis patients appears to reflect modulation of function, and not simply immunosuppression.

Adolescent↗
PubMed1983

T lymphocyte subsets in uveitis.

We evaluated the peripheral T-cell subsets in 32 adult patients with intraocular inflammatory disease and 12 age-matched normal controls by means of the OKT series of monoclonal antibodies in conjunction with the laser cytofluorograph, which quantitatively determines the fluorescence intensity of lymphocytes. We found no statistically significant difference in the ratio of OKT 4-positive (inducer) cells to OKT8-positive (suppressor) cells. However, this ratio was significantly decreased in patients with active posterior uveitis compared with controls (P less than .05). The number of OKT8-positive T lymphocytes in this group was significantly increased (P less than .01), causing a decrease in the OKT4-OKT8 ratio. In patients with positive in vitro cell-mediated responses to the retinal S-antigen, a statistically significant (P less than .05) decrease was found as well only in the patients with active disease.

Adult↗
PubMed1983

Enhancement of the mixed lymphocyte reaction by in vivo treatment of stimulator spleen cells with anti-IgD antibody.

The injection of anti-IgD antibody into mice has been shown to increase the expression of Ia antigens on splenic B cells. These antigens are the most potent lymphocyte-activating determinants (LAD) that trigger proliferation in an H-2-defined mixed lymphocyte reaction (MLR) and may play a role in the recognition of minor lymphocyte-stimulating (MIs) determinants. Therefore, we wished to investigate a possible correlation between apparent quantitative alterations in B cell Ia expression after anti-IgD activation with changes in the functional capacity to present allogeneic major histocompatibility complex (MHC) and MIs antigens to responsive T cells. We observed that the capacity of splenocytes removed 24 hr after the in vivo injection of anti-IgD to stimulate T cell proliferation across an H-2 barrier was most frequently enhanced two- to fourfold when a suboptimal concentration of stimulator cells was used or an early time point in the MLR was examined. In contrast, the capacity of splenocytes to stimulate across an MIsa, d difference after exposure to heterologous or hybridoma anti-IgD antibody often was increased 10-fold or more. Optimal MLR stimulatory capacity was induced by injection of 100 to 200 micrograms of heterologous anti-IgD. Augmented MIs stimulatory capacity of spleen cells peaked 24 hr after such treatment and continued to decline from this value at day 3 and at day 7 after injection. In contrast, the H-2 stimulatory capacity increased 1 day after injection of anti-IgD and remained at that elevated level 3 and 7 days after injection. The spleen cells from B cell-defective (CBA/N x DBA/2)F1 male mice were unaffected in their capacity to stimulate across an MIsa barrier after in vivo anti-IgD treatment; however, spleen cells from phenotypically normal (DBA/2 x CBA/N)F1 male mice after exposure to anti-IgD did evidence a considerably enhanced ability to stimulate in an MIsa-defined MLR. Because anti-IgD antibodies presumably have their major initial effect on surface IgD-bearing B cells, these studies suggest that anti-immunoglobulin-activated B cells may have a role (direct or indirect via interaction with accessory cells) in the presentation of allogeneic MHC and MIs antigens to responsive T cells.

Animals↗
PubMed1983

The asymmetry in idiotype-isotype expression in the response to phosphocholine is due to divergence in the expressed repertoires of Lyb-5+ and Lyb-5- B cells.

The X-linked CBA/N immune defect was used to investigate the roles of Lyb-5- and Lyb-5+ B cells in the memory response to PC-KLH (phosphocholine-conjugated keyhole limpet hemocyanin). (CBA/N X BALB/c)F1 (CB) male mice express the xid mutation and thereby lack the Lyb-5+ B cell subset, whereas their female littermates are normal and express both Lyb-5+ and Lyb-5- B cells. After priming with PC-conjugated hemocyanin (PC-Hy) in complete Freund's adjuvant, female B cells produce three phenotypic sets of PC-KLH-specific antibody. The first set (group I) is dominated by T15+, IgM, IgA, and IgG3, PC-specific antibodies. The second subset (group II) is specific for phenylphosphocholine (PPC), and is dominated by T15-, IgG1, and IgG2 antibodies. The third set (group III) recognizes an epitope(s) composed of both the PPC hapten and carrier determinants. PC-Hy-primed B cells from immune defective CB male mice produce the same number of IgG1 and IgG2 plaque-forming cells (PFC) as do PC-Hy-primed normal female cells, and these PFC are also predominantly T15- and PPC specific (group II). In addition, a significant amount of group III IgG1 and IgG2 antibody is observed in the immune defective male response. In contrast to female B cells, immune defective male B cells produce a low IgM, IgA, and IgG3 memory response that is not composed of PC-specific (group I) antibodies; in fact, most of these antibodies arise from group III precursors and are not inhibited by either PC or PPC. PC-specific antibodies usually represent less than 25% of the anti-PC-KLH response in immune defective mice; however, these PC-specific antibodies are predominantly T15-. These data suggest that the Lyb-5-B cells in both normal and immune defective mice produce the T15-, IgG1, and IgG2 antibodies that dominate the secondary immune response to PC-KLH, and that the Lyb-5+ B cells produce the T15+, IgM, IgA, and IgG3 portion of the secondary response in normal mice. This hypothesis was confirmed by priming normal mice with the R36a strain of Streptococcus pneumoniae or with PC-Hy in saline. These forms of PC-antigen prime only the Lyb-5+ B cell subset. The adoptive transfer of these two B cell sources results in an anti-PC-KLH response that is T15 dominant and totally PC inhibitable.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

The ontogeny and distribution of B cells in normal and mutant immune-defective CBA/N mice: two-parameter analysis of surface IgM and IgD.

A dual-laser fluorescence-activated cell sorter was utilized to study the distribution of the surface IgM and IgD on individual B cells of normal and immune-defective CBA/N mice. Cells from different lymphoid organs and from developing mice were studied. Two major populations of cells were seen. Those with low densities of surface IgM and intermediate-high densities of surface IgD were relatively or totally absent from the bone marrow, spleens, and lymph nodes of adult, immune-defective (CBA/N x DBA/2)F1 male mice, and developed late in ontogeny in the lymphoid organs of normal F1 female mice. By contrast, the second major population, with intermediate-high surface IgM and low surface IgD, was found in highest frequency in the lymphoid organs of immature mice, the bone marrow of adult mice, and the lymphoid organs of F1 male mice compared to F1 female mice at any age. These two major populations of B cells were further subdivided into five groups of cells to better define the surface IgM and IgD characteristics of developing B cells of immune-defective and normal mice. The relationship of these groups of cells to populations defined by other criteria are discussed.

Animals↗
PubMed1983

Analysis of the B cell subpopulations influenced by allogeneic effect factor. I. MHC restricted enhancement of b cell responses to thymic-independent antigens, types 1 and 2, in normal and CBA/N mice.

The ability of allogeneic effect factor (AEF) to enhance the in vitro antibody responses of murine T cell-depleted B cell populations to thymic-dependent (TD) antigens also occurs with thymic-independent (TI) antigens. AEF significantly enhanced the in vitro antibody responses of normal T cell-depleted spleen cell populations to both 2,4,6-trinitophenylated Brucella abortus (TNP-BA), a TI type 1 antigen, and 2,4,6-trinitrophenylated aminoethylcarbamylmethyl-Ficoll (TNP-Ficoll), a TI type 2 antigen. The enhancing activity of AEF on TI responses was analyzed further in immune-defective CBA/N mice that possess only Lyb-5- B cells, and thus fail to respond to TNP-Ficoll, but do respond to TNP-BA and sheep red blood cells (SRBC). AEF was able to reconstitute the in vitro antibody responses of CBA/NT cell-depleted B cell populations to SRBC and to augment the T cell-depleted response to TNP-BA. These data suggest that AEF can enhance the activity of both Lyb-5+ as well as Lyb-5- B cells in their responses to both type 1 and type 2 TI antigens, and to the TD antigen SRBC. This enhancing effect of AEF on the TD and TI responses was MHC restricted for both Lyb-5+ as well as Lyb-5- spleen cells.

Aging↗
PubMed1983

Polyclonal activation of the murine immune system by an antibody to IgD. IV. In vivo activation of B lymphocytes from immune defective CBA/N mice.

Previous studies with BALB/c mice have established that the injection of a goat antibody to IgD (GaM delta) induces splenic B lymphocytes to undergo T-independent, polyclonal increases in cell surface (s) Ia expression, size, and DNA synthesis 1 day after injection, as well as T-dependent maintenance of this activation and differentiation into sIgG1+ cells and IgG1-secreting cells 6 to 7 days after injection. Because B lymphocytes from mice homozygous or hemizygous for the CBA/N X-linked immune defect fail to proliferate in vitro when cultured with soluble anti-Ig antibodies, yet can make in vivo primary antibody responses to T-dependent antigens, we studied the effects of injecting (CBA/N X DBA/2)F1 male mice (immune defective) and (CBA/N X DBA/2)F1 female mice (phenotypically normal) with 800 to 1600 micrograms of GaM delta. B cells from immune defective mice demonstrated definite but distinctly subnormal increases in B cell size, DNA synthesis, and sIa expression 1 to 5 days after GaM delta injection, but by day 7 showed increases in these parameters as well as in the percentages of splenic sIgG1+ cells and IgM-secreting cells that were similar to those exhibited by the immunologically normal mice. However, IgG1 secretion by the immune defective mice was at this time only one-fourth to one-half as great as that observed with normal mice. Our data raises the possibility that the differentiation of B cells into IgG1-secreting cells may be more dependent upon the GaM delta-induced activation steps that are defective in CBA/N mice than is the differentiation of B cells into IgM-secreting cells or into sIgG1 cells.

Animals↗
PubMed1982

Role of the thymus in directing the development of a subset of B lymphocytes.

In an effort to evaluate the role of the thymus in influencing the development of Lyb-5- B lymphocytes, mice expressing both the xid and nu gene defects were studied. Mice expressing either of these defects respond to both trinitrophenylated Brucellus abortus and lipopolysaccharide; whereas mice with the combined defect show markedly suppressed responses. The other abnormalities included: (a) greater than 80 percent diminution of serum Ig levels; (b) significant increase in the number of sIgM+ sIgD- B lymphocytes; (c) reduced expression of IgD on sIgD+ cells; and (d) a strikingly abnormal histology of their lymphoid tissue. Because nu/nu mice that do not express the xid defect appear relatively normal, it would suggest that the development of Lyb-5- B lymphocytes require a thymic influence for normal maturation, whereas, Lyb-5+ B lymphocytes are relatively independent of such influences.

Animals↗
PubMed1982

Distinct alloantigens trigger proliferative or nonproliferative T lymphocyte activation in CBA/N, CBA/J, and C3H mice.

Lymphokine release and proliferation take place during one-way murine mixed leukocyte cultures (MLCs) when responder and stimulator cells differ in H-2 alloantigens, whereas a dissociation of these two functions can be observed where there are incompatibilities in non H-2 alloantigens, It is possible that this dissociation depends on different thresholds of activation of the two responses, or that some non H-2 alloantigens selectively activate lymphokine release or proliferation. To investigate this question we used H-2-matched CBA/N, CBA/J. C3H/HN, (CBA/N x CBA/J)F1, and (CBA/N x C3H/HN)F1 leukocytes, both as responder and stimulator cells. CBA/N mice and the male F1 hybrids obtained from CBA/N mothers carry an X-linked immune defect that results in an arrest of B lymphocyte maturation. In the majority of MLC combinations tested, migration inhibition factor (MIF) release and proliferation took place in parallel. However, CBA/N, but not F1 leukocytes, stimulated MIF release and not proliferation by CBA/J responders, whereas C3H/HN leukocytes stimulated proliferative responses but not MIF release by CBA/J responders. Since proliferation and MIF release have a similar threshold of activation, their dissociation indicates that different non-H-2 alloantigens can specifically activate distinct T cell functions. Moreover, previously unsuspected alloantigen differences between CBA/N and CBA/J are revealed by MIF release.

Animals↗