摘要:

AbstractIn the present study the involvement of the complement system (C) in the clearance of soluble IgA aggregates in the rat was studied. Monoclonal monomeric IgA (mIgA) antibody (which does not activate C) or aggregated polymeric IgA (aIgA; which activates C) were administered intravenously to phosphate‐buffered saline‐treated and complement‐depleted [Cobra venom factor (CVF)‐treated] rats and assessed for clearance from the circulation. In control rats, mIgA was cleared in a biphasic fashion with a first half‐life (T1/2) of 29.5 ± 14.2 min and a second T1/2of 230 ± 176 min. No differences were observed in clearance of mIgA in CVF‐treated rats as compared to PBS‐treated rats. In PBS‐treated rats, aIgA with a size between 20 S and 150 S disappeared very rapidly from the circulation with a first T1/2of 1.1 ± 0.4 min and a second T1/2of 23.2 ± 11.3 min. In CVF‐treated rats the clearance of aIgA was significantly delayed as compared to that in control rats, namely with a first T1/2of 7.3 ± 2.6 min and a second T1/2of 64.2 ± 19.4 min.Immunohistochemical studies of the liver (which is the main site of clearance of aIgA) revealed that Kupffer cells (KC) are mainly responsible for the uptake of aIgA. Furthermore, in PBS‐treated rats aIgA deposition was accompanied by C3 deposition in the KC. In CVF‐treated rats, the percentage of KC containing aIgA was significantly lower during the first 16 min after aIgA administration as compared to PBS treated rats. In addition no detectable C3 was found in KC of CVF‐treated rats. These results indicate that KC play an important role in the clearance of large molecular weight IgA in rats and that C facilitates the clearance of these c

ISSN:0014-2980    

DOI:10.1002/eji.1830210502

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractThe relationship of dendritic cells (DC) isolated from the peripheral blood to those of lymphoid tissue is, in terms of maturation and function, incompletely understood. In our present study, we have explored the molecular basis of adhesion of T cells to blood DC. Analysis of the expression of adhesion receptors on the cell surface of blood DC revealed that these cells express lymphocyte function‐associated antigen (LFA)‐1 (CD11a/18), ICAM‐1 (CD54), LFA‐3 (CD58) and CD44, but are very late antigen (VLA)‐4 (CD49d) and vascular cell‐adhesion molecule (VCAM)‐1 negative. The LFA‐1 pathway was found to play a key role in T cells‐blood DC adhesion; monoclonal antibodies (mAb) against both LFA‐1 and ICAM‐1 strongly inhibited adhesion between those cells. Moreover, a T cell clone from an LFA‐1‐deficient patient showed poor binding to blood DC. The important role of LFA‐1 in T cell‐blood DC adhesion was also supported by the metabolic energy and divalent cation dependence of the interaction. mAb against LFA‐3 and CD2 did not inhibit T cell‐blood DC binding. In contrast to the strong inhibition by antibodies to LFA‐1 and ICAM‐1, antibodies to CD44 enhanced conjugate formation between T cells and blood DC. Together, our results show that the LFA‐1/ICAM‐1 pathway plays a central role in T cell‐blood DC adhesion, a situation like that in T cell adhesion to lymphoid DC. However, unlike lymphoid DC, blood DC do not expr

ISSN:0014-2980    

DOI:10.1002/eji.1830210503

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractGerminal centers contain a proliferating pool of centroblasts which give rise to non‐dividing centrocytes. Centrocytes are programmed to die by apoptosis unless they receive a positive signal for rescue. Rescue,in vivo, is likely to be dependent, initially, on interaction with antigen held on follicular dendritic cells (FDC). A subset of FDC located in that part of the germinal center furthest from centroblasts is particularly rich in CD23. Supernatants containing high levels of soluble CD23 were found not only to encourage the survival of germinal center B cells but also to promote their differentiation toward a plasmacytoid morphology; these activities were diminished following removal of CD23 from the supernatants. Recombinant 25‐kDa CD23 was initially found to be incapable of providing the signal for germinal center cell development but on the addition of interleukin 1α which, by itself, was inactive, rescue and differentiation of germinal center B cells were now achieved. Apoptosis in germinal center cells could also be prevented by the ligation of surface CD40 with monoclonal antibody: however, rescue via this pathway was not accompanied by plasmacytoid differentiation. These findings provide a functional rationale to the high level expression of CD23 found within a discrete subset of FDC and indicate a bifurcation in the development of germinal center B cells following their rescue from apopt

ISSN:0014-2980    

DOI:10.1002/eji.1830210504

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractHuman B lymphocytes that bear the CD5 antigen are relatively abundant in early ontogeny and comprise a small fraction of the B cell population in adults. The CD5 B cell subset has attracted much attention because of its possible involvement in autoimmune disease and certain B cell malignancies. To begin to understand the role of CD5 B cells in disease processes, we have generated a panel of ten human monoclonal B cell lines selected for expression of the CD5 antigen. These cell lines were obtained by Epstein‐Barr virus transformation of B lymphocytes isolated from the spleen, liver and bone marrow of a 19‐week‐old fetus, from cord blood and from peripheral blood of healthy volunteers. In addition, one cell line was isolated from the spleen of a patient with chronic lymphocytic leukemia. Here, we describe the antibody and immunoglobulin VHgene repertoire of this panel of CD5 B cell lines. The results of these experiments show that (a) some but not all CD5 B cell lines secrete polyreactive antibodies that bind to a variety of self‐ and xenoantigens and (b) members of the small VH4, VH5 and VH6 gene families are overrepresented in this panel of cell lines. Nucleotide sequence analysis revealed the expression of VHgene elements that have been previously reported in the preimmune B cell repertoire, in CD5 B cell tumors and in polyreactive ant

ISSN:0014-2980    

DOI:10.1002/eji.1830210505

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractThe elucidation of B lymphocyte development has been partially achieved through genetic models such as the X‐linked immunodeficiency (xid) mutation. We discovered a unique B lymphocyte developmental defect in strain A/WySnJ mice. We used single‐ and two‐color flow cytometry to analyze lymphocytes from A/J and A/WySnJ mice. Adult A/WySnJ mice had a severe B cell deficiency, which was apparent in the spleen, lymph nodes, peritoneum and peripheral blood, compared to adult A/J mice. An ontogeny study revealed that a developmental defect, inhibiting B lymphocyte maturation or differentiation but not B lymphopoiesis, was responsible for the deficiency. This maturational defect blocked the production of B220hi/Iahi/surface IgMloB cells, and was manifested in the adult bone marrow and neonatal spleen, but not the adult spleen. Neither Ly‐1 B cells nor peripheral T cells were apparently affected by the A/WySnJ defect. The B cell immunodeficiency segregated as an autosomal co‐dominant trait in F1and F2mice. We propose that A/WySnJ mice have a novel genetic defect arresting B cell differentiation in adult bone marrow and neonat

ISSN:0014-2980    

DOI:10.1002/eji.1830210506

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractWe have previously reported that a neutral glycolipid (globotriaosylceramide; Gb3) was specifically expressed on Burkitt's lymphoma cells and on a subset of germinal center tonsillar B lymphocytes. Recently the Gb3molecule was recognized as a new B cell differentiation antigen and now defines the CD77 cluster. Here we report an extensive phenotypic and functional characterization of the tonsillar CD77+B lymphocytes. These cells have a low buoyant density and are thus purified using a Percoll gradient. They express various B cell antigens such as CD19, CD20, CD21, CD22 and CD40, as well as the adhesion molecules LFA‐1, LFA‐3 and CD44. They are positive for surface IgM and negative for surface IgD. Although these results suggest a phenotype of activated B cells, the CD77+cells are negative for the classical activation antigens: CD23 (the low‐affinity Fc receptor for IgE), CD25 [the interleukin (IL) 2 receptor α chain] and CD71 (the transferrin receptor). Proliferation and protein synthesis of CD77+cells was measured after stimulation with a range of mitogens and IL. None of the agents tested are able to induce proliferation and protein synthesis with the exception of a combination of recombinant IL 4 plus anti‐CD40 antibody. When examined by electron microscopy, CD77+B lymphocytes present a morphology similar to that of cells undergoing programmed cell death, also called apoptosis (i.e.chromatin condensation, nuclear fragmentation, membrane blebbing). As shown by direct examination of DNA, these CD77+cells are indeed in the process of apoptosis. Treatment of the CD77+cells by recombinant IL 4 and anti‐CD40 antibody prevents apoptosis. All these results suggest that the CD77 molecule defines a B lymphocyte maturation pathway, specific for germinal center, where the cells undergo programmed

ISSN:0014-2980    

DOI:10.1002/eji.1830210507

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractThe present report describes different aspects of two populations of peritoneal cells (PC) obtained from rats injected i.p. 2 h or 24 h previously with a suppressor dose of a purified fraction (FI) of rat male accessory glands (RAG) (FI‐PC2h and FI‐PC24h, respectively). The FI‐PC2h, which are mainly I‐E (OX17) positive and can suppress the autoimmune response to RAG autoantigens, have an elevated phagocytic activity againstCandida albicansand capacity to reduce the dye nitroblue tetrazolium. In contrast, FI‐PC24h, which are mainly I‐A (OX6) positive and can potentiate the autoimmunity to RAG autoantigens, have a diminished capacity to reduce the dye and a diminished phagocytic activity. Moreover, theToxoplasma gondiiappear to have a different effect on both populations. The parasites can invade FI‐PC2h while FI‐PC24h offer resistance toT. gondiiaggression.FI‐PC2h cultured during 22 h (FI‐PC2‐24hin vitro), or PC obtained from syngeneic recipients injected i.p. 22 h previously with FI‐PC2h (FI‐PC2‐24hin vivo) show, as FI‐PC2h, an increase of the I‐E+cells and capacity to induce suppression of the delayed‐type hypersensitivity response to RAG autoantigens when they are injected to syngeneic rats 10 and 3 days prior to the immunization with chemically modified (diazotized arsanilic and sulfanilic acid) RAG in complete Freund's adjuvant.The PC obtained 24 h after injection of irradiated rats with N‐PC plus FI show an increase of I‐E+cells whereas an enhancement of I‐A+cells can be observed when the PC are obtained 24 h after injection of irradiated and bone marrow‐reconstituted rats with N‐PC plus FI.These findings appear to indicate that FI‐PC2h and FI‐PC24h are functionally different and that the population obtained 24 h after injection of FI of RAG could not originate from either the population present 2 h after injection of FI of RAG injection nor from normal PC

ISSN:0014-2980    

DOI:10.1002/eji.1830210508

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractEpitopes defined by monoclonal antibodies (mAb) specific for theBordetella pertussisouter membrane protein P.69 (pertactin) were mapped using a series of amino‐ and carboxy‐terminal deletion mutants expressed inEscherichia coli. mAb were found to bind predominantly to a region of pertactin spanning a (Pro‐Gln‐Pro)5repeat motif and one mAb was found to bind to another region spanning a (Gly‐Gly‐Xaa‐Xaa‐Pro)5repeat motif. To localize further the mAb‐binding sites, a panel of synthetic peptides, a series of 94 overlapping hexameric peptides, and a P.69 30‐amino acid fusion to a hepatitis B core protein (HBcAg‐69), were synthesized. This combined approach has identified the binding site for the mAb BBO5: Pro‐Gly‐Pro‐Gln‐Pro‐Pro; mAb BBO7, E4A8 and E4D7: Ala‐Pro‐Gln‐Pro‐Pro‐Ala‐Gly‐Arg; and mAb BPE3: Thr‐Leu‐Trp‐Tyr‐Ala‐Glu‐Ser‐Asn‐Ala‐Leu‐Ser‐Lys‐Arg. We have used a non‐lethal murine respiratory model ofB.pertussisinfection to investigate the ability of a peptide containing the epitope of the mAb BBO5 to elicit protective immunity. Immunization of mice with the HBcAg‐69 protein prevented growth ofB. pertussisin the lungs compared to mice receiving HBcAg

ISSN:0014-2980    

DOI:10.1002/eji.1830210509

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractThe homeostatic mechanisms controlling B lymphocyte output from bone marrow are not well understood. The present experiments evaluated putative influences of circulating immunoglobulins (Ig) on bone marrow (BM) pre‐B and B cell populations. Injections into normal mice of Ig isolated from normal mouse serum, resulted in a dose‐dependent and reversible reduction in numbers of BM B lineage cells, in particular of small B220+surface IgM−cells. Maximal effects were observed upon injection of isologous polyclonal Ig and were independent of mature T cells. These results suggest a feedback modulation of peripheral Ig on cellular activities in BM B lineage compartments, mediated by mechanisms that seem to involve the variable regions of the Ig mol

ISSN:0014-2980    

DOI:10.1002/eji.1830210510

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractThe nonobese diabetic (NOD) mouse is a relevant model for studying human insulin‐dependent diabetes mellitus (IDDM). The selective destruction of insulin‐secreting cells in this model is subsequent to an autoimmune reaction directed towards the β cells inside the islets of L angerhans of the pancreas. Given the key role played by T cells in the development of IDDM, we investigated a model of IDDM prevention in NOD mice by administration of a monoclonal antibody to the α/β dimer of the T cell receptor for antigen. Our data provide evidence that aiming at the T cell receptor protects against both spontaneous and cyclophosphamide‐induced diabetes in the NOD mouse. Interestingly, potencial clinical application is suggested by the efficient and durable reversal of recent onset diabetes in mice treated with anti‐α/β monoclonal antibody within 1 week following the clinical disco

ISSN:0014-2980    

DOI:10.1002/eji.1830210511

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY