scholarly journals Control of B-lymphocyte function. I. Inactivation of mitogenesis by interactions with surface immunoglobulin and Fc-receptor molecules.

1976 ◽  
Vol 144 (4) ◽  
pp. 882-896 ◽  
Author(s):  
C L Sidman ◽  
E R Unanue
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocyte ◽  
Regulatory Mechanism ◽  
Fc Receptor ◽  
Mouse Spleen ◽  
Lymphocyte Function ◽  
Spleen Cells ◽  
Surface Immunoglobulin

Mouse spleen cells were incubated with anti-Ig antibodies for 1 h, washed, exposed to LPS for 1 h, washed, and their DNA synthetic responses assayed 2 days later. It was shown that the 1-h incubation with anti-Ig antibodies produced a profound, internal, and long lasting state of inactivation in the B cells. Experiments with anti-Ig fragments and other ligands showed that the inactivation occurred optimally when both surface Ig molecules and Fc receptors were bound simultaneously. The role of the classical capping and clearing cycle was also investigated. It was shown that capping and clearing were neither necessary nor sufficient for the inactivation to occur, and that the signals, but only secondarily the ligands themselves, were transmitted across the membrane. Capping and clearing were viewed as a natural regulatory mechanism by which the B cell attempts to clear its membrane of perturbations and signals from the exterior.

Role of B-Lymphocyte Stimulator (BLyS) in Waldenstrom’s Macroglobulinemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 601-601
Author(s):  
Sherine F. Elsawa ◽  
Anne J. Novak ◽  
Deanna M. Grote ◽  
Steven C. Zeismer ◽  
Thomas E. Witzig ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocyte ◽  
Waldenström’S Macroglobulinemia ◽  
Immunoglobulin Production ◽  
B Lymphocyte Stimulator ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

Abstract Waldenstrom’s macroglobulinemia (WM) is a serious and frequently fatal disorder characterized by the production of a monoclonal IgM protein, a lymphoplasmacytic infiltrate in the bone marrow, and associated symptoms including anemia, lymphadenopathy and hyperviscosity. Many of the mechanisms leading to this disease are not yet known. It is clear, however, that there is dysregulation of the balance between cell proliferation and programmed cell death. BLyS (B-lymphocyte stimulator) is a TNF family member expressed by monocytes, neutrophils, macrophages, and dendritic cells. BLyS has been shown to be critical for maintenance of normal B cell development and homeostasis, and has been found to stimulate lymphocyte growth. BLyS is overexpressed in a variety of B-cell malignancies and has been shown to inhibit apoptosis in malignant B-cells. Studies of the effects of BLyS on B cell physiology have shown that it also regulates immunoglobulin secretion. In previous work, we have shown that malignant B cells from patients with WM are able to bind soluble BLyS and variably express the BLyS receptors, BAFF-R, TACI and BCMA. We also found expression of BLyS in bone marrow specimens by immunohistochemistry and elevated serum BLyS levels in patients with WM. The goal of this study was to determine the functional role of BLyS-receptor ligand system in Waldenstrom’s macroglobulinemia and its relevance to the increased immunoglobulin production seen in this disease. Using cells from WM patients, we first examined the ability of BLyS to increase the secretion of IgM by malignant B cells. BLyS, alone or in combination with cytokines that induce plasmacytic differentiation and immunoglobulin production (IL-2, IL-6, IL-10 and IL-12), was found to increase IgM secretion by malignant B cells. Mean baseline IgM levels significantly increased in cells treated with BLyS (p=0.03), cytokines (p=0.0002) and a combination of BLyS and cytokines (p<0.0001). We then determined the effect of BLyS on the survival of malignant B cells using Annexin-V/PI staining. Compared to cells cultured in media alone, BLyS was found to increase viability of malignant B cells from WM patients. Cell viability was normalized relative to the media-alone control and the median relative viability increased significantly compared to controls (median increase 41.2%; range 8 – 46%). Next, we examined the ability of BLyS to modulate cell proliferation using thymidine incorporation. Using WM patient samples, BLyS was found to significantly enhance the proliferation of malignant B cells (p=0.0002). Furthermore, addition of anti-Ig antibody further enhanced the ability of BLyS to promote the proliferation of malignant B cells (p<0.0001). In summary, we have demonstrated that BLyS enhances IgM secretion by malignant B cells from patients with Waldenstrom’s macroglobulinemia. We have also demonstrated the ability of BLyS to enhance the survival and proliferation of malignant B cells. Strategies to inhibit BLyS may potentially have therapeutic efficacy in Waldenstrom’s macroglobulinemia.

scholarly journals Role of IgD in the immune response and tolerance. I. Anti-delta pretreatment facilitates tolerance induction in adult B cells in vitro.

1977 ◽  
Vol 146 (6) ◽  
pp. 1473-1483 ◽  
Author(s):  
D W Scott ◽  
J E Layton ◽  
G J Nossal
Keyword(s):  
Immune Response ◽  
B Cells ◽  
B Cell ◽  
Tolerance Induction ◽  
Spleen Cells ◽  
Cell Compartment ◽  
Immature B Cells

Adult spleen cells from C57BL.Ige mice, which generally are resistant to in vitro tolerance induction in the B-cell compartment, became hyporesponsive (tolerant) when cultured with antigen in the presence of an anti-allotype serum. Both antigen and anti-delta had to be present for this effect, which was hapten-specific and did not occur in C57BL/L mice, which lack the Ig5-1 allotype of the delta-chain detected in this system. Preculture with anti-mu serum plus antigen, in contrast, did not cause tolerance induction in adult spleen B cells of either strain. These results suggest that the surface IgD may act as a failsafe receptor to prevent tolerance induction in adult B cells. Tolerance studies with spleen cells from mice with markedly reduced numbers of IgD+ve cells, because of regimen of repeated injections of anti-delta serum beginning at birth (delta-suppressed mice), confirmed the importance of membrane IgD in preventing tolerance, because such delta-suppressed mice were hypersusceptible to tolerance by antigen alone. Inasmuch as immature B cells lack IgD on their surface, these studies suggest that acquisition of IgD is an important maturational step in the ability of murine B cells to discriminate tolerogenic and immunogenic signals.

scholarly journals Regulation of B Lymphocyte Development by Histone H2A Deubiquitinase BAP1

2021 ◽  
Vol 12 ◽  
Author(s):  
Yun Hsiao Lin ◽  
Yue Liang ◽  
HanChen Wang ◽  
Lin Tze Tung ◽  
Michael Förster ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Cycle Progression ◽  
B Lymphocyte ◽  
Cell Development ◽  
B Cell Development ◽  
Lymphocyte Development ◽  
A Cell ◽  
B Lymphocyte Development

BAP1 is a deubiquitinase (DUB) of the Ubiquitin C-terminal Hydrolase (UCH) family that regulates gene expression and other cellular processes, via deubiquitination of histone H2AK119ub and other substrates. BAP1 is an important tumor suppressor in human, expressed and functional across many cell-types and tissues, including those of the immune system. B lymphocytes are the mediators of humoral immune response, however the role of BAP1 in B cell development and physiology remains poorly understood. Here we characterize a mouse line with a selective deletion of BAP1 within the B cell lineage (Bap1fl/fl mb1-Cre) and establish a cell intrinsic role of BAP1 in the regulation of B cell development. We demonstrate a depletion of large pre-B cells, transitional B cells, and mature B cells in Bap1fl/fl mb1-Cre mice. We characterize broad transcriptional changes in BAP1-deficient pre-B cells, map BAP1 binding across the genome, and analyze the effects of BAP1-loss on histone H2AK119ub levels and distribution. Overall, our work establishes a cell intrinsic role of BAP1 in B lymphocyte development, and suggests its contribution to the regulation of the transcriptional programs of cell cycle progression, via the deubiquitination of histone H2AK119ub.

scholarly journals The BTB-kelch Protein KLHL6 Is Involved in B-Lymphocyte Antigen Receptor Signaling and Germinal Center Formation

2005 ◽  
Vol 25 (19) ◽  
pp. 8531-8540 ◽  
Author(s):  
Jens Kroll ◽  
Xiaozhong Shi ◽  
Arianna Caprioli ◽  
Hong-Hsing Liu ◽  
Claudia Waskow ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
B Lymphocyte ◽  
Antigen Receptor ◽  
Physiological Role ◽  
Antigen Receptor Signaling ◽  
Mouse Mutants

ABSTRACT BTB-kelch proteins can elicit diverse biological functions but very little is known about the physiological role of these proteins in vivo. Kelch-like protein 6 (KLHL6) is a BTB-kelch protein with a lymphoid tissue-restricted expression pattern. In the B-lymphocyte lineage, KLHL6 is expressed throughout ontogeny, and KLHL6 expression is strongly upregulated in germinal center (GC) B cells. To analyze the role of KLHL6 in vivo, we have generated mouse mutants of KLHL6. Development of pro- and pre-B cells was normal but numbers of subsequent stages, transitional 1 and 2, and mature B cells were reduced in KLHL6-deficient mice. The antigen-dependent GC reaction was blunted (smaller GCs, reduced B-cell expansion, and reduced memory antibody response) in the absence of KLHL6. Comparison of mutants with global loss of KLHL6 to mutants lacking KLHL6 specifically in B cells demonstrated a B-cell-intrinsic requirement for KLHL6 expression. Finally, B-cell antigen receptor (BCR) cross-linking was less sensitive in KLHL6-deficient B cells compared to wild-type B cells as measured by proliferation, Ca2+ response, and activation of phospholipase Cγ2. Our results strongly point to a role for KLHL6 in BCR signal transduction and formation of the full germinal center response.

scholarly journals Role of C'3 and Fc receptors in B-lymphocyte activation.

1975 ◽  
Vol 141 (3) ◽  
pp. 647-663 ◽  
Author(s):  
G Möller ◽  
A Coutinho
Keyword(s):  
B Cells ◽  
B Cell ◽  
Polyclonal Antibody ◽  
B Lymphocyte ◽  
Fc Receptors ◽  
Lymphocyte Activation ◽  
Antibody Synthesis ◽  
B Lymphocyte Activation ◽  
Cell Induction

Attempts were made to identify the non-Ig lymphocyte receptor responsible for B-cell induction by antigen and polyclonal B-cell activators (PBA). As a first step, the role of C'3 and Fc receptors was analyzed. It was shown that complement could be fixed onto B cells to such an extent that the lymphocytes could not bind complement-coated red cells, but this did not result in induction of polyclonal antibody synthesis, nor did it inhibit the lymphocytes response to PBA. However, the C'3 receptros possessed a passive focussing role in the induction of polyclonal antibody responses. Thus, PBA that had fixed complement activated polyclonal responses at lower concentrations than the same substances that had not fixed complement. Most likely the dual binding of PBA molecules to B cells by the PBA and the C'3 receptors caused more PBA molecules to be bound to each cell. However, the focussing function of the C'3 receptors was several orders of magnitude smaller than that of the Ig receptors. Analogous studies were carried out with Fc receptors. Binding of different types of antigen-antibody complexes did not cause activation of polyclonal or specific antibody synthesis, nor did it significantly interfere with induction of antibody synthesis by PBA substances.

scholarly journals B-lymphocyte Fc receptor-associated non-H-2 antigens are determined by a single polymorphic locus which is linked of the Mls locus

1977 ◽  
Vol 146 (6) ◽  
pp. 1678-1692 ◽  
Author(s):  
HB Dickler ◽  
A Ahmed ◽  
DH Sachs
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocyte ◽  
Polymorphic Locus ◽  
Fc Receptors ◽  
Fc Receptor ◽  
Recessive Trait ◽  
Ia Antigens ◽  
Lymphocyte Cultures ◽  
Mixed Lymphocyte Cultures

Certain non-H-2 alloantigens are associated with murine B-lymphocyte Fc receptors in that pretreatment of spleen cells with alloantibodies against these antigens inhibited binding of Ig complexes to B-cell Fc receptors. This inhibition was specific in that: (a) as has been shown previously, the Fc portion of the alloantibody was not required to produce inhibition; and (b) antibodies against some non-H-2 antigens but not antibodies against others (including some that were expressed on B cells) caused such inhibition. Backcross experiments revealed that the B-cell Fc receptor-associated non-H-2 antigens were determined by the gene(s) of a single background locus in each of the three strains tested (A/J, B10, and CBA/J). This locus was poly-morphic in that at least four different B-cell Fc receptor:associated non-H-2 antigens were identified (one each in the A/J, B10, and CBAJJ and one antigen shared or crossreactive between the B10 and CBA/J). These antigens were primarily but not exclusively expressed on B lymphocytes as determined by immunofluorescence studies, and on the basis of capping experiments they did not appear to be identical to B-cell Fc receptors. Linkage studies revealed that the locus which determined these antigens was not linked to the albino locus nor the heavy chain allotype locus and expression was neither sex-limited nor an X-linked recessive trait. However, this locus was closely linked but not identical to the Mls locus (apparent recombination frequency 6.8 percent). Thus, two closely linked non-H-2 loci both determine the expression of antigens which have characteristics similar to Ia antigens. One locus is polymorphic and determines the expression of antigens which are primarily expressed on B cells and are specifically associated with the Fc receptors of these cells. The other (Mls locus) determines antigens which are stimulatory in mixed lymphocyte cultures. These observations suggest that there may be a second gene complex which is the analogue of the I region of the H-2 complex.

scholarly journals Regulatory Role of Fc Receptor in mIgM+ B Lymphocyte Phagocytosis in Flounder (Paralichthys olivaceus)

2021 ◽  
Vol 12 ◽  
Author(s):  
Yanbo Hao ◽  
Xiaoqian Tang ◽  
Jing Xing ◽  
Xiuzhen Sheng ◽  
Heng Chi ◽  
...  
Keyword(s):  
B Cell ◽  
B Lymphocytes ◽  
Incubation Time ◽  
B Lymphocyte ◽  
Critical Role ◽  
Fc Receptor ◽  
Control Flow ◽  
Control Group ◽  
Cell Mediated Immunity

Fc receptor (FcR) is an important opsonin receptor on the surface of immune cells, playing an important role in antibody-dependent cell-mediated immunity. Our previous work found that the FcR of flounder showed a marked expression response in phagocytizing IgM+ B cell, which suggested that FcR might participate in regulating Ig-opsonized phagocytosis. In this paper, in order to elucidate the potential role of FcR in mediating phagocytosis of IgM+ B cell, flounder anti-E. tarda serum was prepared and complement-inactivated for the use of E. tarda opsonization, and the sera of healthy flounder were used as control. Flow cytometric analysis showed that the phagocytosis rates of antiserum-opsonized E. tarda in peripheral blood mIgM+ B lymphocytes were significantly higher than the control group, and higher phagocytosis rates of mIgM+ B lymphocyte could be detected with an increasing incubation time ranging from 1 to 5 h. The phagocytosis rates of antiserum-opsonized E. tarda by mIgM+ B lymphocyte for an incubation time of 1, 3 or 5 h were 51.1, 63.0, and 77.5% respectively, which were significantly higher than the phagocytosis rates in the control groups with 40.2, 50.9, and 63.8%, respectively. While the Fc fragment of IgM on the surface of opsonized E. tarda was blocked by rabbit anti-flounder IgM polyclonal antibodies, phagocytosis rates of mIgM+ B lymphocyte decreased significantly compared with the unblocked group. Moreover, the proportion of mIgM+ B lymphocytes with higher intracellular reactive oxygen species (ROS) levels rose to 32.1% from the control level of 23.0% after phagocytosis of antiserum-opsonized E. tarda. FcγRII and Syk were found to be significantly upregulated, while FcγRIII was significantly downregulated in the mIgM+ B lymphocytes post phagocytosis. Furthermore, when FcγRII of mIgM+ B lymphocytes was blocked by the prepared antibodies, their phagocytosis rate of antiserum-opsonized E. tarda was 39.0%, which was significantly lower than the unblocked group of 54.0%. These results demonstrate that FcR plays a critical role in mediating phagocytosis and bactericidal activity of mIgM+ B lymphocytes, which would facilitate an improved understanding of the regulatory roles of FcR in phagocytosis of teleost B lymphocytes.

scholarly journals Anti-Pneumococcal Capsular Polysaccharide Antibody Response and CD5 B Lymphocyte Subsets

2015 ◽  
Vol 83 (7) ◽  
pp. 2889-2896 ◽  
Author(s):  
Leen Moens ◽  
Bert Verbinnen ◽  
Kris Covens ◽  
Greet Wuyts ◽  
Marina Johnson ◽  
...  
Keyword(s):  
B Cells ◽  
Antibody Response ◽  
B Cell ◽  
B Lymphocyte ◽  
Capsular Polysaccharide ◽  
Cell Subset ◽  
Healthy Human ◽  
Cell Subpopulations ◽  
Polysaccharide Antibody

The role of CD19+CD5+and CD19+CD5−B cell subpopulations in the antibody response to pneumococcal capsular polysaccharides (caps-PSs) is controversial. In the present study, we evaluated the role of human CD19+CD5+and CD19+CD5−cell populations in the serotype-specific antibody response to caps-PS. After vaccination of 5 healthy human adults with Pneumovax (23-valent pneumococcal polysaccharide vaccine [PPV23]), IgG anti-caps-PS serotype 4 antibody-producing cells resided mainly in the CD19+CD5−B cell subset, as assessed by enzyme-linked immunosorbent spot (ELISpot) analysis. Moreover, in a humanized SCID mouse model, CD19+CD5−B cells were more effective than CD19+CD5+cells in producing IgG anti-cap-PS antibodies. Finally, an association was found between the level of IgG anti-caps-PS antibodies and the number of CD19+CD5−B cells in 33 humans vaccinated with PPV23. Taken together, our data suggest that CD5 defines a functionally distinct population of B cells in humans in the anti-caps-PS immune response.

scholarly journals B-lymphocyte stimulator (BLyS) stimulates immunoglobulin production and malignant B-cell growth in Waldenström macroglobulinemia

Blood ◽  
2006 ◽  
Vol 107 (7) ◽  
pp. 2882-2888 ◽  
Author(s):  
Sherine F. Elsawa ◽  
Anne J. Novak ◽  
Deanna M. Grote ◽  
Steven C. Ziesmer ◽  
Thomas E. Witzig ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocyte ◽  
Elevated Serum ◽  
B Cell Development ◽  
Immunoglobulin Production ◽  
B Cell Malignancy ◽  
B Lymphocyte Stimulator ◽  
Cell Malignancy

AbstractWaldenström macroglobulinemia (WM) is a serious and frequently fatal B-cell malignancy associated with an elevated monoclonal IgM protein in the serum. Many of the mechanisms leading to this disease are not yet known. B-lymphocyte stimulator (BLyS) is a TNF family member that is critical for maintenance of normal B-cell development and homeostasis. BLyS is overexpressed in a variety of B-cell malignancies and has been shown to inhibit apoptosis in malignant B cells. It also regulates immunoglobulin secretion by normal B cells. To determine the relevance of BLyS in WM, we examined the role of BLyS in WM patient samples. Malignant B cells were found to bind soluble BLyS and variably express the receptors BAFF-R, TACI, and BCMA. We also found expression of BLyS in bone marrow specimens by immunohistochemistry and elevated serum BLyS levels in patients with WM. BLyS, alone or in combination with cytokines that induce immunoglobulin production, was found to increase IgM secretion by malignant B cells. Furthermore, BLyS was found to increase the viability and proliferation of malignant B cells from WM patients. Due to the role of BLyS in WM, strategies to inhibit BLyS may potentially have therapeutic efficacy in these patients.

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