Distribution of lymphocytes identified by surface markers in murine strains with systemic lupus erythematosus-like syndromes (original) (raw)
Related papers
Surface and functional characteristics of B cells from lupus-prone murine strains
Clinical immunology and immunopathology, 1982
B lymphocyte hyperactivity in systemic lupus erythematosus (SLE)-prone mice, originally considered a result of imbalances in T-cell subsets, more recently has been attributed to intrinsic abnormalities of B cells. In our experiments cited here, we used a variety of systems to assess the surface phenotypic and functional characteristics of B cells from several SLE strains (NZB, NZB/W, BXSB, MRL/Mp-lpr/lpr). Generation of Ig isotype diversity follows normal pathways in all these SLE strains. B cells from newborn BXSB and MRL/Mp-lprilpr mice, as in immunologically normal mice, do not reexpress surface Ig (sIg) after modulation with anti-Is. In contrast, B cells of newborn New Zealand mice do reexpress sIg after anti-Ig-induced modulation. The rates at which sIg-anti-Ig complexes cap and become endocytosed in all SLE strains are within normal limits. B cells from SLE strains are stimulated mitogenically by F(ab'), anti-y and lipopolysaccharide with indices no different from those of normal B cells. The ontogenic development of Ia+ and LybS+ cells is normal with the frequency of positive cells and density of alloantigens normal or slightly elevated, respectively. SLE and normal strains are much alike in expression of retroviral envelope gp70 antigen on surfaces of lymphocytes. Anti-gp70 antibodies fail to stimulate mitosis in cells of either SLE or normal strains. However, the frequency of B-cell colony-forming splenocytes is several fold higher in autoimmune mice compared to controls. Expression of acceptor sites for helper messages and of acceptor sites for suppressor messages on B cells is within normal limits in all SLE mice as revealed by the effects of immune response enhancing anti-Lyb3 serum and immune response suppressing anti-Lyb7 serum, respectively. As a whole, these results reaffum the generalized hyperactivity and advanced maturation of B cells of SLE mice but do not reveal any common surface or functional characteristics which might be responsible for the B-cell abnormality.
Autoimmune Diseases, 2013
B lymphocytes are the effectors of humoral immunity, providing defense against pathogens through different functions including antibody production. B cells constitute approximately 15% of peripheral blood leukocytes and arise from hemopoietic stem cells in the bone marrow. It is here that their antigen receptors (surface immunoglobulin) are assembled. In the context of autoimmune diseases defined by B and/or T cell autoreactive that upon activation lead to chronic tissue inflammation and often irreversible structural and functional damage, B lymphocytes play an essential role by not only producing autoantibodies but also functioning as antigen-presenting cells (APC) and as a source of cytokines. In this paper, we describe B lymphocyte functions in autoimmunity and autoimmune diseases with a special focus on their abnormalities in systemic lupus erythematosus.
Clinical Immunology and Immunopathology, 1981
Peripheral blood lymphocytes from 20 patients with systemic lupus erythematosus (SLE) were defective in their ability to secrete immunoglobulin M (IgM) in a pokeweed mitogen (PWM)-stimulated in vitro culture system. To characterize this abnormality, the mononuclear cells were separated into three functional subpopulations: (i) bone marrow-derived (B) cells which secrete immunoglobulin; (ii) a thymus-derived (T) lymphocyte fraction; and (iii) an irradiated T-cell fraction with predominant helper function. Coculture experiments with subsequent radioimmunoassay of the quantity of immunoglobulin secreted allowed comparisons of the immunoregulatory functions of the SLEhelper T, SLE suppressor T, and SLE B cells with functions of control lymphocyte fractions. The major defect defined was an inability of the SLE B cell to secrete normal amounts of IgM This was not due to suppression by monocytes since the removal of phagocytic cells and the addition of separated monocytes to the cultures demonstrated generation of normal helper signals by SLE monocytes. Nor were inadequate numbers of IgM secreting B cells available since limiting dilution studies showed a normal precursor frequency of PWM-stimulatable, IgM secreting SLE B cells. SLE T cells showed a normal helper effect on the secretion of IgM by control B cells. Thus, these in vitro coculture studies designate a primary immunologic defect in SLE to the B cell and not in the suppressor or helper functions of the T cell.
Immunology Today, 1983
B-cell hyperactivity is the general and cardinal feature of murine and human systemic lupus e~ythematosus (SLE), the prototype organ-non-specific autoimmune disease. The defect(s) responsible could be intrinsic to B cells, secondary to T-cell or macrophage abnormalities resulting in excessive help or deficient suppression, or could stem from qualitative/ quantitative abnormalities of autoantigens. Here Argyrios Theofilopoulos and his colleagues review the immunopathological and cellular abnormalities observed in murine lupus and the factors curren@ thought to play a role in normal B-cell proliferation, differentiation and Ig class switching. Next month, in a second article, they discuss abnormalities in B-cell response to and~or overproduction of T-cell-derived accessory signals which may explain the generalized B-cell hyperactivity associated with mouse and human lupus. Derivation of lupus strains and current conclusions The recent availability of two new strains of mice (MRL, BXSB) which, like the NZB and NZB/W F1 mice, spontaneously develop classical SLE-like syndromes, has added greatly to the potential value of murine SLE as an experimental model of generalized autoimmunity 1'2. Now this disease can be observed in mice of three quite different genetic backgrounds (Table I) and essential common denominators identified. In each kind of lupus mouse the disease occurs in two forms: a late-life variety (NZB, BXSB females, MRL/Mp-+/+) that appears during the second year of life; and an acute form (NZB/W F 1
The Journal of Immunology, 2008
Polyclonal B cell activation is a well-described feature of systemic lupus erythematosus (SLE), but the immune mechanisms leading to this activation are unclear. To gain insight into these processes, we extensively characterized the activated peripheral blood B cell populations in SLE. PBMC from lupus patients and healthy controls were stained with various combinations of conjugated Ab to identify distinct peripheral B cell subsets, and activation was assessed by measurement of forward scatter and CD80 or CD86 expression using flow cytometry. SLE patients had altered proportions of several B cell subsets, many of which demonstrated increased activation as assessed by forward scatter. This activation occurred at an early developmental stage, as B cells in the transitional (T2) stage were already significantly larger than those seen in controls. Increased proportions of CD80-or CD86expressing cells were also seen in multiple B cell subsets, with the most striking differences observed in the naive CD27 ؊ CD23 ؉ population. Within the CD23 ؉ subset, increased costimulatory molecule expression was most pronounced in an IgD ؉ IgM low population, suggesting that activation follows Ag engagement. Although controls also had IgD ؉ IgM low CD23 ؉ cells, they were reduced in number and not activated. Thus, there is an altered response to Ig receptor engagement with self-Ags in lupus.
Clinical and Experimental Immunology, 2008
SUMMARYThe precursor frequency for anti-DNA antibody-producing cells in the pre-immune B cell repertoire was investigated in young female BALB/c and NZW mice, and in young and aged female NZB ± NZWFl (B/WF1) mice. Spleen cells from these mice were diluted serially and stimulated polyclonally in vitro with lipopolysaccharide (LPS) and IL-4 to induce both IgM and IgG1 production. The results demonstrated that there existed virtually no difference in precursor frequency for IgM anti-DNA antibody-producing cells between normal and lupus mice, confirming previous observations made by other investigators. In contrast, the number of precursors for IgG 1 anti-DNA antibody-producing cells was much higher in young and old B/WF1 mice than in normal mice. These results suggest that the high frequency of precursors for IgG1 anti-DNA antibody-producing cells in the pre-immune B cell repertoire of B/WF1 mice is a crucial factor for the pathogenesis of systemic lupus erythematosus.
Clinical and Experimental Immunology, 2008
SUMMARYPrecursor frequencies for anti-DNA-secreting B cells were estimated in six healthy donors and 18 SLE patients with active and inactive disease. Precursors for IgG anti-dsDNA-secreting B cells were exclusively detected in SLE patients (73% of active patients and one inactive patient, 0.01 – 0.99% of IgG-producing B cells). These frequencies were in the same order of magnitude as frequencies of precursors for IgG anti-tetanus toxoid, which were detectable in three healthy volunteers after booster vaccination (0.07–0.8% of IgG-producing B cells), but not before (<001%). Precursors for IgG anti-ss-DNA secreting B cells were observed in 33% of healthy donors and in 78% of SLE patients (0.01 – 0.32% of IgG-producing B cells). Only patient-derived IgG anti-DNA clones cross-reacted with (33%) or were monoreactive to dsDNA (12%). Precursors for IgM anti-DNA-secreting B cells were observed in healthy donors and SLE patients in comparable frequencies and with similar reactivities wit...
B lymphocytes and systemic lupus erythematosus
Current Rheumatology Reports, 2003
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by B cell hyperactivity in association with autoantibodies, most prominently those directed to components of the cell nucleus. The source of the antigens that drive B cell responses in SLE is unknown, although recent studies suggest mechanisms by which the self-antigens become immunogenic and stimulate responses. Among these mechanisms, abnormalities in the generation of apoptotic cells or their clearance may increase the availability of nuclear antigens to drive responses. In addition, autoantibody crossreactivity may promote induction of responses to disparate antigens, foreign and self, and enable a single autoantibody to cause disease by crossreactive binding. In addition to reflecting increased exposure to self-antigen, autoantibody responses in SLE may result from abnormalities in B cell signaling and regulation by cytokines. New approaches to therapy aim to abrogate autoantibody production by targeting specific steps in B cell activation, including blockade of T cell costimulation.