-
Immunologic Research 1988Studies from a number of laboratories have firmly established the potential of surface immunoglobulin-generated signals in B lymphocyte activation. While clearly there... (Review)
Review
Studies from a number of laboratories have firmly established the potential of surface immunoglobulin-generated signals in B lymphocyte activation. While clearly there are multiple ways of activating B lymphocytes, some of which may not involve surface immunoglobulin, it is clear that crosslinking of surface immunoglobulin whether by antigen or antireceptor antibody can generate signals relevant to B cell activation. Although considerable insight into the mechanism of transduction of mIg-generated signals across the plasma membrane has been realized, a molecular explanation for linking inositol phospholipid hydrolysis to changes within the cytoplasm and nucleus of the B cell is still speculative. A more rigorous definition of the PKC and calcium components of the mIg signal transduction pathway are critical for a thorough understanding of the mechanism of signal transduction by this receptor. The use of tumor cell models allowing selection of mutants within the signalling pathway(s) will be invaluable to fully defining the critical molecular and biochemical events involved in B cell activation.
Topics: Animals; Antigens; B-Lymphocytes; Calcium; In Vitro Techniques; Lymphocyte Activation; Protein Kinase C; Receptors, Antigen, B-Cell; Receptors, Immunologic; Tumor Cells, Cultured
PubMed: 3292672
DOI: 10.1007/BF02918097 -
Journal of Immunology Research 2020Antibody-secreting cells (ASCs) play a fundamental role in humoral immunity. The aberrant function of ASCs is related to a number of disease states, including autoimmune... (Review)
Review
Antibody-secreting cells (ASCs) play a fundamental role in humoral immunity. The aberrant function of ASCs is related to a number of disease states, including autoimmune diseases and cancer. Recent insights into activated B cell subsets, including naïve B cell to ASC stages and their resultant cellular disturbances, suggest that aberrant ASC differentiation occurs during autoimmune diseases and is closely related to disease severity. However, the mechanisms underlying highly active ASC differentiation and the B cell subsets in autoimmune patients remain undefined. Here, we first review the processes of ASC generation. From the perspective of novel therapeutic target discovery, prediction of disease progression, and current clinical challenges, we further summarize the aberrant activity of B cell subsets including specialized memory CD11cT-bet B cells that participate in the maintenance of autoreactive ASC populations. An improved understanding of subgroups may also enhance the knowledge of antigen-specific B cell differentiation. We further discuss the influence of current B cell therapies on B cell subsets, specifically focusing on systemic lupus erythematosus, rheumatoid arthritis, and myasthenia gravis.
Topics: Animals; Autoimmune Diseases; B-Lymphocyte Subsets; B-Lymphocytes; Cell Differentiation; Humans; Immunity, Humoral; Immunologic Memory; Immunotherapy; Lymphocyte Activation
PubMed: 32280720
DOI: 10.1155/2020/9518137 -
Scandinavian Journal of Immunology Mar 1989The monoclonal antibody (MoAb) B1B6 to human leucocyte sialoglycoprotein, CD43, induces aggregation of T cells and delivers progression signals early during activation...
The monoclonal antibody (MoAb) B1B6 to human leucocyte sialoglycoprotein, CD43, induces aggregation of T cells and delivers progression signals early during activation of both T and B cells in the presence of primary activators of protein kinase C. In this report we further studied the role of CD43 in human B-cell activation and differentiation. About 5-10% of resting tonsillar B cells are CD43+. In the presence of TPA or antibodies to CDw40, the proportions of CD43+ cells drastically increased. The expression was optimal on day 3 of culture, when up to 80% and 50%, respectively, were CD43+. Whereas MoAb B1B6 together with TPA induced a three- to fivefold higher proliferative response as compared to TPA alone, antibodies to CDw40 did not synergize with MoAb B1B6 in B-cell proliferation. Tonsillar populations depleted of CD43+ B cells responded with lower proliferation to TPA alone or to TPA and B1B6 or anti-CDw40 antibodies. MoAb B1B6 did not affect the production of IgM or IgG as induced by pokeweed mitogen in the presence of autologous T cells, from either peripheral blood or tonsillar B cells. Neither did it affect the IgG production from the CD43+ BSF-2 sensitive Epstein-Barr virus-transformed lymphoblastoid cell line CESS. The results show that CD43 is upregulated on B cells during activation. Furthermore, CD43+ B cells are included in the population which responds to signals delivered by TPA, anti-CD43 or anti-CDw40 antibodies, and the proliferation of this population is not merely due to an expansion of the small population of CD43+ cells present among these cells. Moreover, the epitopes recognized by MoAb B1B6 are not involved in the differentiation of and ultimate Ig-secretion from activated B cells.
Topics: Antibodies, Monoclonal; Antigens, CD; Antigens, Differentiation; B-Lymphocytes; Cell Differentiation; Cell Line; Drug Synergism; Humans; Immune Sera; Immunoglobulin G; Leukosialin; Lymphocyte Activation; Phenotype; Pokeweed Mitogens; Sialoglycoproteins; Signal Transduction; Tetradecanoylphorbol Acetate
PubMed: 2785706
DOI: 10.1111/j.1365-3083.1989.tb01134.x -
Journal of Basic and Clinical... Jan 2020Background Urate in its crystal form is a known danger-associated molecular pattern, which after its internalization activates cells of the innate immune system....
Background Urate in its crystal form is a known danger-associated molecular pattern, which after its internalization activates cells of the innate immune system. However, by inducing lipid raft sequestration and clustering of membrane-bound proteins with immunoreceptor tyrosine-based activation motifs, urate crystals can also activate cells of the innate immune system without previous internalization. Also, urate crystals trigger T-cell receptor signal transduction and induce T-cell proliferation. In this study, we evaluated whether urate crystals can also initiate B-cell receptor (BCR) signal transduction and promote B-cell proliferation. Methods B cells were isolated from the blood of 10 individuals and cultured with or without urate at a concentration of 10 mg/dL, at which crystallization occurs. Phosphorylated Igα (CD79A) and c-Myc were assessed by Western blotting and B-cell proliferation with BrdU assay. Results Urate increased the level of phosphorylated Igα, a component of the BCR complex. Phosphorylation of Igα is the very proximal event in BCR signal transduction. Also, urate increased the expression of c-Myc, an essential transcription factor for BCR-induced B-cell proliferation. Finally, urate induces B-cell proliferation. Conclusions Urate crystals trigger BCR signal transduction and induce B-cell proliferation. The clinical significance of urate-induced B-cell activation remains to be elucidated.
Topics: Adult; Antioxidants; B-Lymphocytes; Cell Proliferation; Female; Humans; Leukocytes, Mononuclear; Liquid Crystals; Male; Middle Aged; Phosphorylation; Receptors, Antigen, B-Cell; Signal Transduction; Uric Acid
PubMed: 31927516
DOI: 10.1515/jbcpp-2019-0054 -
European Journal of Immunology Oct 1990The effects of the immunosuppressants cyclosporin A (CsA), FK506 and rapamycin have been compared using murine B cells activated with a variety of mitogens. FK506 is a... (Comparative Study)
Comparative Study
The effects of the immunosuppressants cyclosporin A (CsA), FK506 and rapamycin have been compared using murine B cells activated with a variety of mitogens. FK506 is a macrolide antibiotic that has been recently shown to inhibit T cell activation by a mechanism that appears similar to that of CsA. Rapamycin is a macrolide structurally related to FK506 whose mechanism of T cell suppression appears to be distinct from that of FK506 and CsA. While CsA and FK506 were found to preferentially inhibit B cell activation caused by stimuli which induce a rise in intracellular calcium, rapamycin partially inhibited activation by all stimuli tested, including those which are not associated with a calcium flux. All three compounds were found to inhibit cell cycle progression within the G1 phase; however, the rapamycin-sensitive event within G1 was completed earlier than the G1 events inhibited by CsA and FK506. In addition, inhibition of anti-IgM-activated B cells with CsA and FK506, but not with rapamycin, resulted in cell death. These data suggest that although CsA, FK506 and rapamycin are all inhibitors of B cell activation, the inhibitory activity of rapamycin can be clearly distinguished from that of CsA and FK506. Although the suppressive effects of CsA and FK506 on B cell proliferation were nearly identical in this study, their biological activities were distinguishable since FK506, but not CsA, could antagonize rapamycin-mediated suppression.
Topics: Animals; Anti-Bacterial Agents; Antibodies, Monoclonal; B-Lymphocytes; Cell Cycle; Cell Survival; Cyclosporins; Female; Histocompatibility Antigens Class II; Immunosuppressive Agents; Kinetics; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Polyenes; Sirolimus; Tacrolimus
PubMed: 1700753
DOI: 10.1002/eji.1830201017 -
Journal of Immunology (Baltimore, Md. :... Feb 2007Signaling by the BCR involves activation of several members of the Ras superfamily of small GTPases, among which is Ras itself. Ras can control the activity of multiple...
Signaling by the BCR involves activation of several members of the Ras superfamily of small GTPases, among which is Ras itself. Ras can control the activity of multiple effectors, including Raf, PI3K, and guanine nucleotide exchange factors for the small GTPase Ral. Ras, Raf, and PI3K have been implicated in a variety of processes underlying B cell development, differentiation, and function; however, the role of Ral in B lymphocytes remains to be established. In this study, we show that Ral is activated upon BCR stimulation in human tonsillar and mouse splenic B lymphocytes and in B cell lines. Using signaling molecule-deficient B cells, we demonstrate that this activation is mediated by Lyn and Syk, Btk, phospholipase C-gamma2, and inositol-1,4,5-trisphosphate receptor-mediated Ca(2+) release. In addition, although Ral can be activated by Ras-independent mechanisms, we demonstrate that BCR-controlled activation of Ral is dependent on Ras. By means of expression of the dominant-negative mutants RasN17 and RalN28, or of RalBPDeltaGAP, a Ral effector mutant which sequesters active Ral, we show that Ras and Ral mediate BCR-controlled transcription of c-fos. Furthermore, while not involved in NF-kappaB activation, Ras and Ral mediate BCR-controlled activation of JUN/ATF2 and NFAT transcription factors. Taken together, our data show that Ral is activated upon BCR stimulation and mediates BCR-controlled activation of AP-1 and NFAT transcription factors. These findings suggest that Ral plays an important role in B cell development and function.
Topics: B-Lymphocytes; Cell Line, Tumor; Cells, Cultured; Humans; Mutation; NFATC Transcription Factors; Palatine Tonsil; Receptors, Antigen, B-Cell; Transcription Factor AP-1; ral GTP-Binding Proteins; ras Proteins
PubMed: 17237388
DOI: 10.4049/jimmunol.178.3.1405 -
Nouvelle Revue Francaise D'hematologie 1988Two-color FACS analysis was used to study phenotypic subset and activation markers on circulating B (tumor) cells of 21 patients with chronic B-lymphocytic leukemia...
Two-color FACS analysis was used to study phenotypic subset and activation markers on circulating B (tumor) cells of 21 patients with chronic B-lymphocytic leukemia (B-CLL). Patients with clinically active (progressive) disease differed from patients with stable disease: B cells from the former patient category showed a significantly increased expression of the activation antigen 1D11 and FN99(CD9), and a decreased expression of the FN1 B subset marker. No clinical associations were observed using the CD23, CD25, 4F2, Ba, Bac-1 or FN50 markers. Functional studies showed that the B cells from both clinical categories of patients responded equally well with DNA synthesis when optimally triggered and supplied with T cell factors. However, B-CLL cells from patients with progressive disease secreted significantly higher levels of IgM in response to phorbol ester. The present experiments thus show that differences exist in the activation of B-CLL cells in vivo and that these patterns are correlated with disease activity. Further, the maximal in vitro proliferative capacity of individual tumor cells is similar, whereas differences in accessory T cell functions may exist between patients.
Topics: Antigens, Differentiation, B-Lymphocyte; B-Lymphocytes; DNA; Humans; Immunoglobulin M; Leukemia, Lymphocytic, Chronic, B-Cell; Leukocyte Count; Lymphocyte Activation; Phenotype
PubMed: 3265498
DOI: No ID Found -
European Journal of Immunology Mar 2022BOB.1/OBF.1 is a lymphocyte-specific transcriptional co-activator of octamer-dependent transcription. It regulates the expression of genes important for lymphocyte...
BOB.1/OBF.1 is a lymphocyte-specific transcriptional co-activator of octamer-dependent transcription. It regulates the expression of genes important for lymphocyte physiology together with the Oct-1 and Oct-2 transcription factors. So far, BOB.1/OBF.1 has been studied in conventional knockout mice, whereby a function of BOB.1/OBF.1 in B but also in T cells was described. The main characteristic of BOB.1/OBF.1-deficient mice is the complete absence of germinal centers. However, it is entirely unsolved at which stage of B-cell development BOB.1/OBF.1 expression is essential for germinal center formation. Still, it is not known whether defects observed late in B-cell development of BOB.1/OBF.1-deficient mice are merely a consequence of defective early B-cell development. To answer the question, whether BOB.1/OBF.1 expression is required before or during the process of germinal center formation, we established a mouse system, which allows the conditional deletion of BOB.1/OBF.1 at different stages of B-cell development. Our data reveal a requirement for BOB.1/OBF.1 during both early antigen-independent and late antigen-dependent B-cell development, and further a requirement for efficient germinal center reaction during complete B-cell ontogeny. By specifically deleting BOB.1/OBF.1 in germinal center B cells, we provide evidence that the failure to form germinal centers is a germinal center B-cell intrinsic defect and not exclusively a consequence of defective early B-cell maturation.
Topics: Animals; B-Lymphocytes; Cell Differentiation; Germinal Center; Lymphocyte Activation; Mice; Octamer Transcription Factor-2; Trans-Activators; Transcription Factors
PubMed: 34918350
DOI: 10.1002/eji.202149333 -
Trends in Immunology Oct 2003The transcriptional co-activator OCA-B [for Oct co-activator from B cells, also known as OBF-1 (OCT-binding factor-1) and Bob1] is not required for B-cell genesis but... (Review)
Review
The transcriptional co-activator OCA-B [for Oct co-activator from B cells, also known as OBF-1 (OCT-binding factor-1) and Bob1] is not required for B-cell genesis but does regulate subsequent B-cell development and function. OCA-B deficient mice show strain-specific, partial blocks at multiple stages of B-cell maturation and a complete disruption of germinal center formation in all strains, causing humoral immune deficiency and susceptibility to infection. OCA-B probably exerts its effects through the regulation of octamer-motif controlled gene expression. The OCA-B gene encodes two proteins of distinct molecular weight, designated p34 and p35. The p34 isoform localizes in the nucleus, whereas the p35 isoform is myristoylated and is bound to the cytoplasmic membrane. p35 can traffic to the nucleus and probably activates octamer-dependent transcription, although this OCA-B isoform might regulate B cells through membrane-related signal transduction.
Topics: Animals; Antibody Formation; B-Lymphocytes; Humans; Immune System; Signal Transduction; Trans-Activators
PubMed: 14552839
DOI: 10.1016/j.it.2003.08.002 -
Journal of Immunology (Baltimore, Md. :... Aug 1985The B1 molecule is a 32,000 m.w. phosphorylated cell surface protein expressed exclusively by B cells from the mid pre-B until the plasma cell stage of differentiation....
The B1 molecule is a 32,000 m.w. phosphorylated cell surface protein expressed exclusively by B cells from the mid pre-B until the plasma cell stage of differentiation. Two monoclonal antibodies (gamma 2a and mu) reactive with this molecule were used to assess the role of B1 in B cell activation, proliferation, and differentiation. The anti-B1 antibodies at concentrations ranging from 0.1 to 100 micrograms/ml significantly inhibited B cell proliferation induced by anti-mu antibodies, Staphylococcus aureus Cowan strain 1, activated T cells, and Epstein Barr virus. Although capable of inhibiting proliferation, anti-B1 antibody in soluble form or coupled to beads did not activate B cells or induce proliferation. Antibodies of comparable isotypes or against other B cell-restricted antigens, including B2, B4, B5, and HB-5, did not inhibit activation. Pretreatment of B cells with anti-B1 antibody did not inhibit activation, indicating that B cells had to be cultured with anti-B1 antibody for anti-B1-mediated inhibition to occur. Maximum inhibition was obtained when anti-B1 antibody was added at the initiation of culture. In agreement with this, growth factor-dependent proliferation of preactivated B cells was not inhibited by anti-B1 antibodies. Comparable inhibition of B cell activation was noted with antibodies reactive with class II antigens of the major histocompatibility complex with the exception that anti-B1 antibody inhibited immunoglobulin secretion in pokeweed mitogen assays, whereas anti-DR antibody did not. These results suggest that the B1 molecule may serve a central role in the regulation of B cell activation and differentiation.
Topics: Adult; Antibodies, Monoclonal; Antigens, Differentiation, B-Lymphocyte; Antigens, Surface; B-Lymphocytes; Binding, Competitive; Cell Differentiation; Growth Substances; Humans; Interphase; Lymphocyte Activation; Microspheres; Time Factors
PubMed: 3925015
DOI: No ID Found