Synergistic Cooperation Between T and B Lymphocytes from Old Mice in the Production of Auto-Anti-Idiotypic Antibody Regulation in Adult Irradiated Hosts

Author(s):  
Myron R. Szewczuk

ABSTRACTThe effect of age on the ability of B lymphocytes and thymus cells from donors of various ages to be capable of producing an anti-idiotype-blocked, hapten-augmentable PFC was studied by adoptive cell transfer techniques. Lethally irradiated mice were reconstituted with syngeneic B lymphocytes and thymus cells from donors of various ages. Recipients were immunized with trinitrophenylated bovine gamma globulin (TNP-BGG) one or seven days after cell transfer. Splenic IgG anti-TNP plaque-forming cell (PFC) responses were assayed in the absence and presence of hapten for anti-idiotype (Id)-blocked, hapten-augmentable PFC, 14 days after immunization. It was found that the B lymphocyte population from 2 month old donors together with thymus cells from donors of various ages (2 to 19 months) were incapable of reconstituting mice to produce anti-Id-blocked, hapten-augmentable PFC. Similar results were obtained when mice were reconstituted with thymus cells from 2-month-old donors together with B cells from donors of various ages (2 to 14 months). In contrast, mice reconstituted with B cells plus thymus cells from the same 8-month or older donors produced a significantly high percentage of anti-Id-block, hapten augmentable PFC. Mice reconstituted with B cells from 8 months or older donors plus thymus cells from donors of various ages (8 to 19) months also produced a significantly high percentage of hapten-augmentable PFC. Experiments with B cells and thymus cells from 2-or 8-month old donors parked in lethally irradiated 2-or 8-months old recipients for 7 days revealed that neither lymphocytes from old donors or old recipients were capable of inducing the appearance of anti-Id-blocked, hapten-augmentable PFC in the lymphocyte population from 2-month-old donors. Thus, the results of this study indicate syner-gistic co-operation between B lymphocytes and thymus cells from old donors for the production of auto-anti-idiotypic antibody regulation with age. This production of auto-anti-Id antibody with age seems not to be an induced maturation event but perhaps an intrinsic property unique to lymphocytes from old donors.

1978 ◽  
Vol 147 (1) ◽  
pp. 196-206 ◽  
Author(s):  
D H Sherr ◽  
M R Szewczuk ◽  
G W Siskind

Lethally irradiated mice reconstituted with adult thymus cells and neonatal or fetal liver cells produce an anti-2,4-dinitrophenyl or anti-bovine gamma globulin response of restricted heterogeneity of affinity in comparison with the response of mice reconstituted with B cells from adult donors. In addition, mice reconstituted with day 15 fetal B cells and adult thymus cells produce relatively few indirect plaque-forming cells (PFC). It was found that B cells acquire the capacity to produce a heterogeneous response, of predominantly indirect PFC within 7 days of transfer only when thymus cells are transferred along with the B cells. B cells from fetal or neonatal donors transferred without young adult thymus cells develop the capacity to generate indirect PFC within 13 days after transfer to adult recipients, but continue to produce a response of restricted heterogeneity of affinity for up to 28 days after transfer. Thus, it has been shown that cells present in the thymus facilitate, or are necessary for the functional maturation of B lymphocytes. Furthermore, the data suggest that maturation of the B-cell population to produce a heterogeneous response is controlled independently of its maturation to be capable of producing indirect PFC.


1989 ◽  
Vol 1 (1) ◽  
pp. 27-35 ◽  
Author(s):  
R D Sanderson ◽  
P Lalor ◽  
M Bernfield

Lymphopoietic cells require interactions with bone marrow stroma for normal maturation and show changes in adhesion to matrix during their differentiation. Syndecan, a heparan sulfate-rich integral membrane proteoglycan, functions as a matrix receptor by binding cells to interstitial collagens, fibronectin, and thrombospondin. Therefore, we asked whether syndecan was present on the surface of lymphopoietic cells. In bone marrow, we find syndecan only on precursor B cells. Expression changes with pre-B cell maturation in the marrow and with B-lymphocyte differentiation to plasma cells in interstitial matrices. Syndecan on B cell precursors is more heterogeneous and slightly larger than on plasma cells. Syndecan 1) is lost immediately before maturation and release of B lymphocytes into the circulation, 2) is absent on circulating and peripheral B lymphocytes, and 3) is reexpressed upon their differentiation into immobilized plasma cells. Thus, syndecan is expressed only when and where B lymphocytes associate with extracellular matrix. These results indicate that B cells differentiating in vivo alter their matrix receptor expression and suggest a role for syndecan in B cell stage-specific adhesion.


Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1972-1976 ◽  
Author(s):  
BJ Chen ◽  
J Epstein

Abstract The mononuclear cells in the blood of myeloma patients have been reported to contain a high proportion of phenotypically abnormal myeloma B lymphocytes. These cells have been proposed to constitute the drug-resistant proliferative myeloma cell compartment. To determine the extent of B lymphocyte involvement, the proportion of clonotypic cells among the CD19-expressing cells from myeloma patients was estimated by quantitative polymerase chain reaction analysis of the third complementarity determining region (CDR3). The results indicate that the B lymphocytes constitute, on average, 6% of blood mononuclear cells, and that only a minor fraction of these are clonally related to the myeloma cells. While the small number of circulating clonal cells is not incompatible with their proposed role as a reservoir of proliferating myeloma progenitors, the majority of the B cells appear not to be clonally related to the myeloma cells.


2004 ◽  
Vol 78 (22) ◽  
pp. 12489-12496 ◽  
Author(s):  
Nathalie Parez ◽  
Antoine Garbarg-Chenon ◽  
Cynthia Fourgeux ◽  
Françoise Le Deist ◽  
Annabelle Servant-Delmas ◽  
...  

ABSTRACT Immunity to human group A rotavirus (RV), a major cause of viral gastroenteritis in infants, involves B lymphocytes that provide RV-specific antibodies. Additionally, some arguments suggest that naive B cells could be implicated in the first steps of the immune response against RV. The aim of our study was to analyze the interaction of VP6 and VP7 RV capsid proteins with human B cells depending on the immune status of the individual, i.e., naive or RV experienced. For this purpose, a two-color virus-like particle flow cytometry assay was devised to evaluate the blood B-lymphocyte reactivity to VP6 and VP7 proteins from healthy RV-exposed adults, recently infected infants, and neonates at birth. Both VP6 and VP7 interactions with B cells were mediated by surface immunoglobulins and probably by their Fab portions. VP7-reactive B lymphocytes were mainly detected from RV-experienced patients and almost exclusively in the CD27-positive memory cell fraction. Conversely, VP6-reactive B lymphocytes were detected at similar and high frequencies in adult, infant, and neonate samples. In adult samples, VP6 reacted with about 2% of the CD27-negative (CD27neg) naive B cells. These results demonstrated that the VP6 RV protein interacted with a large fraction of naive B lymphocytes from both adults and neonates. We propose that naive B cell-VP6 interaction might influence the strength and quality of the acquired immune response and should be considered for elaborating RV vaccine strategies.


1998 ◽  
Vol 187 (5) ◽  
pp. 753-762 ◽  
Author(s):  
Conrad C. Bleul ◽  
Joachim L. Schultze ◽  
Timothy A. Springer

Migration of mature B lymphocytes within secondary lymphoid organs and recirculation between these sites are thought to allow B cells to obtain T cell help, to undergo somatic hypermutation, to differentiate into effector cells, and to home to sites of antibody production. The mechanisms that direct migration of B lymphocytes are unknown, but there is evidence that G protein–coupled receptors, and possibly chemokine receptors, may be involved. Stromal cell– derived factor (SDF)-1α is a CXC chemokine previously characterized as an efficacious chemoattractant for T lymphocytes and monocytes in peripheral blood. Here we show with purified tonsillar B cells that SDF-1α also attracts naive and memory, but not germinal center (GC) B lymphocytes. Furthermore, GC B cells could be converted to respond to SDF-1α by in vitro differentiation into memory B lymphocytes. Conversely, the migratory response in naive and memory B cells was significantly reduced after B cell receptor engagement and CD40 signaling. The receptor for SDF-1, CXC chemokine receptor 4 (CXCR4), was found to be expressed on responsive as well as unresponsive B cell subsets, but was more rapidly downregulated on responsive cells by ligand. Finally, messenger RNA for SDF-1 was detected by in situ hybridization in a layer of cells surrounding the GC. These findings show that responsiveness to the chemoattractant SDF-1α is regulated during B lymphocyte activation, and correlates with positioning of B lymphocytes within a secondary lymphoid organ.


1985 ◽  
Vol 161 (6) ◽  
pp. 1581-1586 ◽  
Author(s):  
Y Ron ◽  
J Sprent

Despite earlier evidence to the contrary, it has recently been claimed that most B lymphocytes, including lymph node (LN) and thoracic duct B cells, are short-lived cells of recent marrow origin. To seek direct information on this question, we transferred unprimed LN or thoracic duct B cells from normal mice to xid mice, i.e., mice unresponsive to the T-independent antigen, trinitrophenyl (TNP)-Ficoll. At varying periods after B cell transfer the recipients were challenged with TNP-Ficoll; anti-TNP plaque-forming cells were assayed in the spleen 6 d later. The results showed that the B cell recipients retained responsiveness to TNP-Ficoll for at least 3 mo after transfer. Responsiveness increased within the first 3 wk but then remained relatively constant. These findings imply that, at least for TNP-Ficoll-reactive cells, B cells residing in LN and thoracic duct lymph are not short-lived cells of recent marrow. Indeed, the data suggest that once the pool of recirculating B cells is fully formed in adult mice, further input of newly formed cells from the marrow into the recirculating pool is very limited.


Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1972-1976 ◽  
Author(s):  
BJ Chen ◽  
J Epstein

The mononuclear cells in the blood of myeloma patients have been reported to contain a high proportion of phenotypically abnormal myeloma B lymphocytes. These cells have been proposed to constitute the drug-resistant proliferative myeloma cell compartment. To determine the extent of B lymphocyte involvement, the proportion of clonotypic cells among the CD19-expressing cells from myeloma patients was estimated by quantitative polymerase chain reaction analysis of the third complementarity determining region (CDR3). The results indicate that the B lymphocytes constitute, on average, 6% of blood mononuclear cells, and that only a minor fraction of these are clonally related to the myeloma cells. While the small number of circulating clonal cells is not incompatible with their proposed role as a reservoir of proliferating myeloma progenitors, the majority of the B cells appear not to be clonally related to the myeloma cells.


2021 ◽  
Vol 15 (2) ◽  
pp. 17-22
Author(s):  
A. V. Martynova ◽  
T. V. Popkova ◽  
A. P. Aleksankin ◽  
G. I. Gridneva ◽  
E. V. Gerasimova ◽  
...  

Objective: to evaluate changes in T- and B-lymphocyte subpopulations at different stages of rheumatoid arthritis (RA).Patients and methods. The study included 53 patients with a definite RA diagnosis according to the 2010 ACR/EULAR criteria (mean age 54.2 [47; 62] years). Group 1 included 27 patients (25 women and 2 men) without history of synthetic disease modifying anti-rheumatic drugs (sDMARDs) intake, group 2 included 26 patients (22 women and 4 men) receiving sDMARDs (methotrexate or leflunomide). The control group consisted of 29 healthy volunteers (23 women and 6 men), the median age was 58.5 [53; 62] years. In all participants flow cytofluorometry according to the standard technique with immunophenotyping of T- and B-lymphocytes was performed.Results and discussion. Compared to controls, patients in group 1 who had not previously received sDMARDs showed a transient increase in "switched" memory B-cells, transient B-cells, and plasmablasts, which was not observed in patients of group 2 (on sDMARDs therapy). Patients with advanced RA showed a statistically significant decrease in the absolute and relative number of memory B-cells, the absolute and relative number of "switched" B-lymphocytes, as well as the number of plasmablasts and transient cells. In RA patients, a statistically significant rela tionship was established between the number of swollen joints and the level of plasmablasts (r=0.51), memory cells (r=0.54), and "switched" B-cells (r=0.41), p< 0,05 in all cases. There were no statistically significant changes in other subpopulations of B-lymphocytes and the profile of T-lymphocytes.Conclusion. Changes in the B-lymphocyte profile are characteristic of different stages of RA. At an early stage, there is an increase in the number of transient B-lymphocytes, plasmablasts and plasmocytes, and in the advanced stage, a decrease in the level of certain populations of B-lymphocytes, such as memory B-cells and "switched" B-lymphocytes. It can be assumed that the ineffectiveness of sDMARDs is associated with a change in the population composition of B-lymphocytes, which requires further study.


2021 ◽  
Vol 22 (24) ◽  
pp. 13560
Author(s):  
Benjamin Y. F. So ◽  
Desmond Y. H. Yap ◽  
Tak Mao Chan

Membranous nephropathy (MN) is an important cause of nephrotic syndrome and chronic kidney disease (CKD) in adults. The pathogenic significance of B cells in MN is increasingly recognized, especially following the discovery of various autoantibodies that target specific podocytic antigens and the promising treatment responses seen with B cell depleting therapies. The presence of autoreactive B cells and autoantibodies that bind to antigens on podocyte surfaces are characteristic features of MN, and are the result of breaches in central and peripheral tolerance of B lymphocytes. These perturbations in B cell tolerance include altered B lymphocyte subsets, dysregulation of genes that govern immunoglobulin production, aberrant somatic hypermutation and co-stimulatory signalling, abnormal expression of B cell-related cytokines, and increased B cell infiltrates and organized tertiary lymphoid structures within the kidneys. An understanding of the role of B cell tolerance and homeostasis may have important implications for patient management in MN, as conventional immunosuppressive treatments and novel B cell-targeted therapies show distinct effects on proliferation, differentiation and reconstitution in different B cell subsets. Circulating B lymphocytes and related cytokines may serve as potential biomarkers for treatment selection, monitoring of therapeutic response and prediction of disease relapse. These recent advances in the understanding of B cell tolerance in MN have provided greater insight into its immunopathogenesis and potential novel strategies for disease monitoring and treatment.


Blood ◽  
1980 ◽  
Vol 55 (1) ◽  
pp. 67-70 ◽  
Author(s):  
MD Appay ◽  
J Bariety ◽  
R Bretton

Abstract In six normal subjects, no surface immunoglobulins were detected on blood lymphocytes containing bundle-shaped tubular (BST) inclusions, after incubation with anti-human IgM peroxidase-labeled Fab'2 fragments. These Fab'2 fragments from pepsin-digested sheep anti-human immunoglobulins revealed human mu kappa, and lambda chains. These results suggest that the BST inclusions do not belong to B lymphocytes but belong to T cells and/or a third lymphocyte population, including K cells and precursors of T and B cells.


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