Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.32 (bromelain)
 1,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MRL/MP-lpr/lpr (MRL/lpr) mice are known to provide a good model for the study on the pathogenesis of systemic lupus erythematosus with massive involvement of abnormal T lymphocytes in the spleen and lymphonodes. However, a direct role of B cells of MRL/lpr mice in autoimmune responses is not clear until this time. In the present study, to investigate the characteristic of B cells of the mice, we tried to establish a B cell clone after hybridization between splenic B cells of these mice and 2.52 M, a HAT selective medium sensitive mutant B cell line in the presence of polyethylene glycol and dimethyl sulfoxide and examined its response to autoantigens. MRL27.4, a subclone of a resulting hybridoma, expressed IgM, B220, IKk, ICAM-1, and LEA-1 on the cell membrane as well as CD5 molecules by analysis with flow microfluorometory (FMF). Also, MRL27.4 was shown to exhibit rosette formation against blood cells treated with bromelain (Br-RBC) at a frequency of more than 95%, and to express DNA-receptor (DNA-R) on its surface by FMF analysis with biotin-labeled ssDNA. In contrast, the parental 2.52 M did not form rosettes with Br-RBC and the expression of DNA-R on the cell membrane of 2.52 M was significantly less compared with that of MRL27.4. Interestingly, MRL27.4 produced a high titer of IgM-anti-ssDNA antibodies and IL-6 after treatment with the purified RBC membrane or immobilized DNA. On the other hand, the parental 2.52 M neither produce IgM-anti-ssDNA antibodies nor IL-6 under the same conditions. The results suggest that MRL27.4 is an autoantigen reactive B cell clone derived from MRL/lpr mice and its surface DNA-R, by itself, function to autoantigens. In this process, there might be an autocrine network mediated by IL-6. In conclusion, MRL27.4 provides a good model for the study on the direct function of B cells of MRL/lpr mice during abnormal immune responses to autoantigens.
 ...
PMID:[Functional analysis of an autoantigen reactive B cell clone derived from MRL/MP-lpr/lpr mice]. 912 24

Spleen, lymph node, and peripheral blood lymphocytes from healthy guinea pigs (gp) were examined for their ability to produce polyreactive autoantibodies to a battery of self-antigens and to cryptic determinants (phosphatidylcholine) on bromelain-treated mouse red blood cells (Br-MRBC). The mouse monoclonal antibody (Mab) 8BE6 anti-gp pan-T (CD5) marker was used for identification of CD5+ B1 cells by the plaque-forming assay (PFC), immunofluorescence, complement-mediated cytotoxicity, and immunocytochemistry. The detection of CD5+ cells by the 8BE6 Mab depended on the method used. They were better demonstrated by cytolysis and immunocytochemistry than by FACS analysis. By the latter method, the level of the CD5+ B cell subpopulation was associated neither with the age of the gp nor with the organ examined. Similarly wide ranges of PFC were detected in untreated or LPS-treated animals regardless of age and organ. The vast majority of the LPS-stimulated IgM antibody-secreting B lymphocytes reacting with the Br-MRBC, and those producing natural autoantibodies, did not bind the 8BE6 Mab.
 ...
PMID:CD5+ and CD5- B1-like lymphocytes in healthy guinea pig. 934 96

Mice expressing the X-linked immunodeficiency (xid) mutation lack functional Bruton's tyrosine kinase and were shown to be specifically deficient in peritoneal B-1 lymphocytes. We have previously shown that IL-9, a cytokine produced by TH2 lymphocytes, promotes B-1 cell expansion in vivo. To determine whether IL-9 overexpression might compensate the xid mutation for B-1 lymphocyte development, we crossed xid mice with IL-9-transgenic mice. In this model, IL-9 restored normal numbers of mature peritoneal B-1 cells that all belonged to the CD5(-) B-1b subset. Despite this normal B-1 lymphocyte number, IL-9 failed to restore classical functions of B-1 cells, namely, the production of natural IgM Abs, the T15 Id Ab response to phosphorylcholine immunization, and the antipolysaccharide humoral response against Streptococcus pneumoniae. By using bromelain-treated RBC, we showed that the antigenic repertoire of these IL-9-induced B-1b lymphocytes was different from the repertoire of classical CD5(+) B-1a cells, indicating that the lack of B-1 function by B-1b cells is associated with distinct Ag specificities. Taken together, our data show that B-1b cell development can restore the peritoneal B-1 population in xid mice but that these B-1b cells are functionally distinct from CD5(+) B-1a lymphocytes.
 ...
PMID:IL-9-induced expansion of B-1b cells restores numbers but not function of B-1 lymphocytes in xid mice. 1512 95

Growing awareness of the pathophysiological importance of B cells for antiphospholipid antibody syndrome (APS), particularly those expressing the T cell marker CD5, has recently led to the proposal that their tolerance may be used as a method to reduce specific antibody (Ab) production. B cell tolerance has indeed become one of the most exciting developments in the treatment of this disease. Based on their production of multispecific Ab, these CD5+ B lymphocytes, also referred to as B-1 cells, are thought to account for most of the AutoAb in autoimmune murine models. Raised numbers of circulating CD5+ B cells correlate with high levels of anti-phospholipid (PL) Ab in some APS patients, and participate in altered immunity of women with recurrent spontaneous abortion. These findings are not surprising in view of the cross-reaction with PL of anti-bromelain-treated erythrocyte Ab secreted by these cells. Transgenic animals have, however, shown that B lymphocytes contribute to such disorders through a variety of characteristics other than Ab production. Indeed, owing to the role of the CD5 molecule in the maintenance of clonal anergy, increased proportions of B-1 cells may merely reflect their defective regulation through CD5 itself. Various B cell receptor (BCR)-associated transmembrane glycoproteins are also involved in the behavior of the cells. These include CD19 which amplifies the message, and CD22 which dampens down the BCR signaling. In addition, B lymphocytes may act as potent antigen-presenting cells for autoantigens, all the more because they secrete an excess of autocrine-acting interleukin-10 in autoimmune states. Furthermore, by modifying the specificity of their BCR, not only in the bone-marrow, but also in the secondary lymphoid organs, autoreactive B cells may initiate new immunoglobulin rearrangements. It is interesting that self-reactive Ab-making cells present with such rearrangements. Finally, B cells have the capacity to polarize into B effector (Be)-1 and Be-2, with different cytokine patterns that regulate the levels of T helper (Th)-1 and Th-2, respectively. Such a cytokine might be defective in nonorgan-specific autoimmune diseases. In conclusion, B lymphocytes are required for the initiation of anti-self Ab-associated disorders, such as APS. Their classical view in the biology of immune responses to self as autoAb secreting cells turns out to be rather naive, and an essential role for B lymphocytes may not be producing autoAb.
 ...
PMID:The antiphospholipid syndrome as a model for B cell-induced autoimmune diseases. 1550 66


<< Previous 1 2