scholarly journals ONTOGENY OF B LYMPHOCYTES

1974 ◽  
Vol 139 (5) ◽  
pp. 1125-1141 ◽  
Author(s):  
Michael C. Gelfand ◽  
Gerald J. Elfenbein ◽  
Michael M. Frank ◽  
William E. Paul
Keyword(s):  
B Lymphocytes ◽  
B Lymphocyte ◽  
Genetic Difference ◽  
Backcross Progeny ◽  
Soluble Antigen ◽  
B Cell Differentiation ◽  
Adult Mice ◽  
The Difference ◽  
Antigen Antibody ◽  
Akr Mice

Many bursa-equivalent (B) lymphocytes of adult mice bear surface Ig and receptors for C3. The frequency of Ig-bearing cells increases rapidly immediately after birth, but these cells lack complement (C) receptors. Lymphocytes bearing C receptors are not found in the spleens of BALB/c, DBA/2, and C57BL/6 mice until 2 wk of age and do not attain substantial numbers until 3–4 wk of age. In AKR mice, a lag between appearance of Ig-bearing and complement receptor lymphocytes (CRL) is also observed but it is of much shorter duration. AKR mice have a frequency of CRL at 2 wk of age of 28% in comparison to a frequency of 4.8% for DBA/2 mice. The difference in frequency between young and adult mice and between "low" and "high CRL" strains cannot be explained by a nonspecific inability to form rosettes as similar results are obtained with soluble antigen-antibody-complement complexes. Analysis of CRL frequency in (AKR x DBA/2)F1 mice and F1 x parental backcross progeny suggests that two independent genes control the rate of appearance of CRL. Furthermore, the genetic difference in the ontogeny of CRL is recapitulated in the repopulation of the B-lymphocyte line in adult-irradiated mice restored with syngeneic bone marrow. Thus, the "CRL genes" described here appear to control B-cell differentiation throughout life.

scholarly journals Negative selection of human germinal center B cells by prolonged BCR cross-linking.

1996 ◽  
Vol 183 (5) ◽  
pp. 2075-2085 ◽  
Author(s):  
L Galibert ◽  
N Burdin ◽  
C Barthélémy ◽  
G Meffre ◽  
I Durand ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Germinal Center ◽  
B Lymphocyte ◽  
Calcium Flux ◽  
Cross Linking ◽  
B Cell Differentiation ◽  
Selection Of

The antigen receptors on T and B lymphocytes can transduce both agonist and antagonist signals leading either to activation/survival or anergy/death. The outcome of B lymphocyte antigen receptor (BCR) triggering depends upon multiple parameters which include (a) antigen concentration and valency, (b) duration of BCR occupancy, (c) receptor affinity, and (d) B cell differentiation stages. Herein, using anti-immunoglobulin kappa and lambda light chain antibodies, we analyzed the response of human naive, germinal center (GC) or memory B cells to BCR cross-linking regardless of heavy chain Ig isotype or intrinsic BCR specificity. We show that after CD40-activation, anti-BCR (kappa + gamma) can elicit an intracellular calcium flux on both GC and non-GC cells. However, prolonged BCR cross-linking induces death of CD40-activated GC B cells but enhances proliferation of naive or memory cells. Anti-kappa antibody only kills kappa + GC B cells without affecting surrounding gamma + GC B cells, thus demonstrating that BCR-mediated killing of GC B lymphocytes is a direct effect that does not involve a paracrine mechanism. BCR-mediated killing of CD40-activated GC B cells could be partially antagonized by the addition of IL-4. Moreover, in the presence of IL-4, prestimulation through CD40 could prevent subsequent anti-Ig-mediated cell death, suggesting a specific role of this combination in selection of GC B cells. This report provides evidence that in human, susceptibility to BCR killing is regulated along peripheral B cell differentiation pathway.

scholarly journals Studies on the clonal origin of multiple myeloma. Use of individually specific (idiotype) antibodies to trace the oncogenic event to its earliest point of expression in B-cell differentiation.

1979 ◽  
Vol 150 (4) ◽  
pp. 792-807 ◽  
Author(s):  
H Kubagawa ◽  
L B Vogler ◽  
J D Capra ◽  
M E Conrad ◽  
A R Lawton ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
B Cell ◽  
B Lymphocytes ◽  
Plasma Cell ◽  
B Lymphocyte ◽  
B Cell Differentiation ◽  
Clonal Origin ◽  
B Lineage

IgA myeloma proteins of kappa- and lambda-types were isolated from two patients. These were used to produce and purify anti-idiotype antibodies of both broad (myeloma-related) and narrow (individual myeloma) specificities. The anti-idiotype antibodies were conjugated with fluorochromes and used as immunofluorescent probes to trace in the patients clonal expansion at different levels of B-cell differentiation. Our results (a) confirm that B lymphocyte precursors in IgA plasma-cell myelomas are involved in the malignant process, (b) show that B lymphocytes of the malignant clone include those expressing each of the major heavy-chain isotypes, mu, delta, gamma, and alpha, and (c) provide strong circumstantial evidence that pre-B-cell members of the malignant clone are also increased in frequency. T cells expressing idiotypic determinants were not detected. These findings argue that the initial oncogenic event may occur in a B-stem cell and is not influenced through stimulation by antigen. An interesting association was the increased frequency of related clones of B lymphocytes as detected by their reactivity with anti-idiotype antibodies of broad specificity. Neither plasma cell nor pre-B-cell members of these related clones were increased in frequency. Anti-idiotype antibodies or helper T cells reactive with myeloma-related idiotypes could be responsible for this phenomenon. We discuss other implications of these findings and speculate that all of the various phenotypes of B-lineage malignancies may result from oncogenic processes affecting stem cell targets.

scholarly journals Crosslinkage of B lymphocyte surface immunoglobulin by anti-Ig or antigen induces prolonged oscillation of intracellular ionized calcium.

1987 ◽  
Vol 166 (2) ◽  
pp. 601-606 ◽  
Author(s):  
H A Wilson ◽  
D Greenblatt ◽  
M Poenie ◽  
F D Finkelman ◽  
R Y Tsien
Keyword(s):  
B Cell ◽  
B Lymphocytes ◽  
Cell Activation ◽  
B Lymphocyte ◽  
Accessory Cell ◽  
Base Line ◽  
B Cell Differentiation ◽  
B Cell Activation ◽  
Technical Approach ◽  
Indicator Dyes

Our results indicate that B lymphocytes stimulated with anti-Ig or antigen exhibit repetitive [Ca2+]i transients which persist for hours. The magnitude of these transients favors an important and ongoing role for [Ca2+]i elevation in antigen driven B cell activation. Repetitive Ca2+ transients may prove to be a prevalent mechanism of Ca2+ signaling. In preliminary experiments (with L. E. Samelson and R. D. Klausner), we have observed Ca2+ transients in cloned T cells stimulated with antigen. Woods et al. have described repetitive free Ca2+ transients in hepatocytes stimulated with extracellular ligands promoting glycogenolysis, and suggest that the intervals of base-line [Ca2+]i levels explain the absence of mitochondrial overload in chronically stimulated cells. These considerations apply equally to B lymphocytes and recommend caution in delineating the range of Ca2+-mediated functions by prolonged coculture of cells with Ca2+ ionophores. Our experiments were done in a simple recording chamber with one cell type. No cell interactions were observed. Given the variety of indicator dyes now available, the technical approach we present, augmented by a more sophisticated recording chamber, is a potentially powerful tool for examining the intrinsic, and T- or accessory cell-dependent, physiology of B cell differentiation.

scholarly journals COMPLEMENT-DEPENDENT RELEASE OF IMMUNE COMPLEXES FROM THE LYMPHOCYTE MEMBRANE

1973 ◽  
Vol 138 (3) ◽  
pp. 495-507 ◽  
Author(s):  
Gary W. Miller ◽  
Paul H. Saluk ◽  
Victor Nussenzweig
Keyword(s):  
Cell Membrane ◽  
B Lymphocytes ◽  
Immune Complexes ◽  
Mammalian Species ◽  
Normal Serum ◽  
Soluble Antigen ◽  
Lymphocyte Membrane ◽  
Alternate Pathway ◽  
Extensive Degradation ◽  
Antigen Antibody

Soluble antigen-antibody-complement complexes bound to mouse B lymphocytes are rapidly released from the cell membrane in the presence of normal serum from several mammalian species. The release is not the result of antigen-antibody dissociation or extensive degradation of the complexes. However, the released complexes have been altered because they will no longer bind to fresh lymphocytes. The release is not the result of lymphocyte damage mediated by complement. It is complement-dependent, and is generated either preferentially or exclusively via the alternate pathway, since it occurs in C4-deficient serum, is Mg++ but not Ca++ dependent, and requires C3 proactivator. C3 inactivator is not involved. The release activity of the serum, once generated, is unstable at 37°C. The release of complexes from the lymphocyte membrane by serum provides a convenient assay for the functioning of the alternate pathway in the mouse and in other species.

scholarly journals Interactions between lymphocyte membrane molecules. I. Interaction between B lymphocyte surface IgM and Fc IgG receptors requires ligand occupancy of both receptors.

1981 ◽  
Vol 153 (5) ◽  
pp. 1329-1343 ◽  
Author(s):  
H B Dickler ◽  
M T Kubicek
Keyword(s):  
B Lymphocyte ◽  
Surface Membrane ◽  
Specific Interaction ◽  
Normal Serum ◽  
Membrane Receptors ◽  
Soluble Antigen ◽  
Lymphocyte Surface ◽  
Igg Receptors ◽  
Antigen Antibody

The independent B lymphocyte surface membrane receptors IgM and Fc IgG receptors were evaluated for interactions using immunoflourescence. Ligand [F(ab')2 anti-mu]-induced capping of surface IgM resulted in capping of Fc IgG receptors only if the latter were occupied during the capping process by: (a) soluble antigen-antibody complexes that themselves provided insufficient cross-linking to result in capping; or (b) monomeric IgG at physiologic concentrations (or less) either purified or as normal serum. Ligand-induced capping of Fc IgG receptors did not result in capping of surface IgM occupied by monomeric F(ab') anti-mu. Control experiments showed that ligand binding to or capping of only one of these two receptors has no effect on the other, and that there were no cross-reactions. The interaction appears specific in that ligand-induced capping of surface IgM did not induce capping of ligand-occupied surface IgD or I-A antigens. Thus, there appears to be a specific interaction between ligand-bound surface IgM and ligand-bound Fc IgG receptors on the B lymphocyte surface. The results also indicate that binding of monomeric IgG produces a reversible alteration in the Fc IgG receptor leading to association with ligand-bound surface IgM. Because Fc IgG receptors are continuously exposed to monomeric IgG in vivo, these results suggest that whenever surface IgM is involved in a B lymphocyte response to an immunologic stimulus, the Fc IgG receptor is also involved.

scholarly journals T lymphocyte-dependent B lymphocyte proliferative response to antigen. I Genetic restriction of the stimulation of B lymphocyte proliferation.

1981 ◽  
Vol 153 (4) ◽  
pp. 871-882 ◽  
Author(s):  
H Y Tse ◽  
J J Mond ◽  
W E Paul
Keyword(s):  
T Lymphocytes ◽  
B Lymphocytes ◽  
T Lymphocyte ◽  
Lymphocyte Proliferation ◽  
B Lymphocyte ◽  
Antigen Specificity ◽  
Apparent Lack ◽  
The Face ◽  
Stimulation Of

For the purpose of examining more closely the interaction between T and B lymphocytes, we have developed an in vitro T lymphocyte-dependent B lymphocyte proliferation assay. Proliferation of B lymphocytes in response to antigen was found to depend on the presence of primed T lymphocytes; the B lymphocytes could be derived from nonprimed animals. It appears that these B cells were nonspecifically recruited to proliferate. This nonspecific recruitment, however, was found to be Ir-gene restricted in that B lymphocytes from B10.S mice, which are genetic nonresponders to the polymer Glu60-Ala30-Tyr10 (GAT), could not be stimulated by GAT-primed (responder X nonresponder) F1 T cells. The apparent lack of antigen specificity in the face of Ir gene-restricted T-B interaction may have important implications in our understanding of the recognition unit(s) on T lymphocytes.

Antigen-antibody complexes bound to B-lymphocyte Fcγ receptors regulate B-lymphocyte differentiation

1985 ◽  
Vol 95 (2) ◽  
pp. 368-379 ◽  
Author(s):  
Ferenc Uher ◽  
Marinus C. Lamers ◽  
Howard B. Dickler
Keyword(s):  
B Lymphocyte ◽  
Fcγ Receptors ◽  
Lymphocyte Differentiation ◽  
Antigen Antibody

scholarly journals CYTOTOXICITY MEDIATED BY SOLUBLE ANTIGEN AND LYMPHOCYTES IN DELAYED HYPERSENSITIVITY

1968 ◽  
Vol 128 (6) ◽  
pp. 1237-1254 ◽  
Author(s):  
Nancy H. Ruddle ◽  
Byron H. Waksman
Keyword(s):  
Lymph Node ◽  
Genetic Difference ◽  
Specific Antigen ◽  
Delayed Hypersensitivity ◽  
Target Cells ◽  
Soluble Antigen ◽  
Rat Embryo ◽  
Egg Albumin ◽  
Lymph Node Cells ◽  
Electronic Particle Counter

In the presence of specific antigen, lymph node cells from inbred rats with delayed hypersensitivity to tuberculoprotein, bovine gammaglobulin, and egg albumin produced progressive destruction of monolayers of rat embryo fibroblasts in tissue culture, first apparent at 48 hr and maximal at 72 hr. The effect was specific and did not depend on a genetic difference between the lymph node cells and target cells. It required antigen concentrations equal to or greater than 1.25 µg/ml and lymphocyte: target cell ratios of approximately 10 or 20:1. It could be evaluated both by a plaquing technique and by cell enumeration with an electronic particle counter.

Fetal liver pro-B and pre-B lymphocyte clones: expression of lymphoid-specific genes, surface markers, growth requirements, colonization of the bone marrow, and generation of B lymphocytes in vivo and in vitro

1992 ◽  
Vol 12 (2) ◽  
pp. 518-530
Author(s):  
R Palacios ◽  
J Samaridis
Keyword(s):  
B Cell ◽  
B Lymphocytes ◽  
Stromal Cells ◽  
B Lymphocyte ◽  
Germ Line ◽  
Fetal Liver ◽  
Rag 1 ◽  
B Cell Precursors

We describe here the development and characterization of the FLS4.1 stromal line derived from 15-day fetal liver of BALB/c embryos and defined culture conditions that efficiently support the cloning and long-term growth of nontransformed B-220+ 14-day fetal liver cells at two stages of B-cell development, namely, pro-B lymphocytes (immunoglobulin [Ig] genes in germ line configuration) and pre-B cells (JH-rearranged genes with both light-chain Ig genes in the germ line state). All B-cell precursor clones require recombinant interleukin-7 (rIL-7) and FLS4.1 stromal cells for continuous growth in culture, but pro-B lymphocyte clones can also proliferate in rIL-3. None proliferate in rIL-1, rIL-2, rIL-4, rIL-5, rIL-6, or leukemia inhibitory factor. FLS4.1 stromal cells synthesize mRNA for Steel factor but not for IL-1 to IL-7; all pro-B and pre-B clones express c-Kit, the receptor for Steel factor, and a c-Kit-specific antibody inhibits the enhanced proliferative response of fetal liver B-220+ B-cell precursors supported by FLS4.1 stromal cells and exogenous rIL-7 but does not affect that promoted by rIL-7 alone. Northern (RNA) blot analysis of the expression of the MB-1, lambda 5, Vpre-B, c mu, RAG-1, and RAG-2 genes in pro-B and pre-B clones show that transcription of the MB-1 gene precedes IgH gene rearrangement and RNA synthesis from c mu, RAG-1, RAG-2, lambda 5, and Vpre-B genes. All clones at the pre-B-cell stage synthesize mRNA for c mu, RAG-1, and RAG-2 genes; transcription of the lambda 5 and Vpre-B genes seems to start after D-to-JH rearrangement in B-cell precursors, indicating that the proteins encoded by either gene are not required for B-cell progenitors to undergo D-to-JH gene rearrangement. These findings mark transcription of the MB-1 gene as one of the earliest molecular events in commitment to develop along the B-lymphocyte pathway. Indeed, both pro-B and pre-B clones can generate in vitro and in vivo B lymphocytes but not T lymphocytes; moreover, these clones do not express the CD3-gamma T-cell-specific gene, nor do they have rearranged gamma, delta, or beta T-cell antigen receptor genes.

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