The Journal of molecular and cellular immunology : JMCI最新文献

{"title":"Inducible Ig heavy chain switching in an IgM+ Ly-1 B cell line. Evidence for a state of switch commitment.","authors":"J Braun,&nbsp;W J Krall,&nbsp;M E Clark,&nbsp;H L Govan,&nbsp;U Chen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have analyzed the pattern of immunoglobulin (Ig) heavy chain isotype secretion in AJ9, a cloned, IgM+ murine B lymphocyte cell line. Upon induction by a variety of lymphokines and polyclonal B-cell activators, AJ9 cells express multiple subclasses of IgG and IgA in addition to IgM. In certain cases, mature isotype is restricted--e.g., IL-5 predominantly elicits production of IgG2 and IgA, a restriction also observed in short-term lymphocyte cultures. In other cases (e.g., anti-IgM plus 8-mercaptoguanosine, a polyclonal B-cell activator) production of mature isotypes is unrestricted. Under optimal conditions, only a low abundance of secreted Ig and low frequency of secreting cells (less than 0.5%) were detected. A serial cloning assay was devised to define the pattern of isotype switching in induced cells and their progeny. We expected to observe a progressive limitation of progeny to expression of single mature isotypes. Surprisingly, nearly all subclones of the induced cells were found to produce a range of mature isotypes. Sequential cloning in basal medium revealed that this induced phenotype persisted for more than a month (greater than 40 generations). Throughout this period, the abundance of mature isotype production remained low, and membrane Ig was exclusively of the IgM isotype. We interpret this induced response to reflect an intermediate state of B-cell differentiation, in which cells become committed to the switching process, but are not adequately stimulated to efficiently complete the process required for expression of mature isotypes. These findings are discussed in regard to the control of the switching process, and their possible relevance to the memory state of B cells.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"4 2","pages":"105-19"},"PeriodicalIF":0.0,"publicationDate":"1988-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14281562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Membrane expression of IgG but not maturation to secretion requires DNA replication.","authors":"L Forni,&nbsp;M Björklund,&nbsp;A Coutinho","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In this work we have addressed two questions. Does switch recombination occur before membrane expression or only concomitantly with induction to high rate synthesis and secretion of IgG? Does interleukin-4 induce switch to IgG1 or maturation of already switched cells? To answer these questions we used the DNA synthesis inhibitor hydroxyurea (HU) to analyze the requirements for DNA replication in the induction of membrane expression or high rate secretion of all IgG subclasses by cultures of mouse spleen cells stimulated by lipopolysaccharide (LPS) and supplemented with IL-4, the absolute numbers of cells bearing membrane bound IgG was always decreased by HU, indicating that immunoglobulin class switching requires DNA replication. IL-4 did not augment the numbers of cells expressing any IgG isotype. In contrast, the number of high rate secretors of all IgG isotypes was not affected by HU, except in the case of IgG3 and IgG2b shortly after stimulation. Addition of IL-4 resulted in an increased number of secretory cells, and also this effect was resistant to HU. Thus, for any isotype, treatment with HU or IL-4 increased the frequency of secretory cells relative to the surface positive population. This data indicates that: 1) IL-4 is a broad range, non isotype-specific maturation factor for LPS-activated B cells; 2) induction to high rate secretion has a negative effect on proliferation; and 3) immunoglobulin class switch, but not induction to secretion of any immunoglobulin isotype, requires DNA replication, suggesting that switch recombination had to occur before expression of IgG in the membrane-bound form.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"4 2","pages":"59-70"},"PeriodicalIF":0.0,"publicationDate":"1988-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14394121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoreactive T cells with atypical MHC restriction from MRL-lpr/lpr mice: forbidden clones revisited.","authors":"Y Naparstek,&nbsp;K Baur,&nbsp;M D Reis,&nbsp;L Breitman,&nbsp;T W Mak,&nbsp;R S Schwartz,&nbsp;M P Madaio","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>MRL-lpr/lpr mice spontaneously develop a lethal form of systemic lupus erythematosus associated with massive lymphadenopathy, polyclonal B-cell activity, autoantibody production and antibody-dependent tissue injury. The sequence of events leading to B-cell proliferation and pathogenic autoantibody production are not clearly defined--abnormalities of both B and T cells have been observed. Isolation of individual T-cell clones would facilitate analysis of the cellular events involving both B and T cells that lead to autoantibody production. For this purpose, an autoreactive T-cell line (ARTC-1) was derived from the splenocytes of an unimmunized MRL-lpr/lpr mouse and maintained in culture by stimulation with syngeneic antigen presenting cells, without exogenous antigens. By T-cell receptor analysis it was demonstrated that ARTC-1 cells developed as a clone even through no attempt was made to clone them in vitro: Southern blot analysis of ARTC-1 revealed a single rearrangement of the TcR beta chain locus with the other TcR beta chain gene remaining in the germline configuration. Northern blot analysis confirmed these findings and demonstrated that ARTC-1 utilized C beta 1 J beta 1.3 exclusively. ARTC-1 had atypical MHC requirements for activation: antigen-presenting cells bearing both I-Ak and I-Ek major histocompatibility complex class II antigens were required for maximal proliferation of the ARTC-l clone. Activated ARTC-l secreted soluble factors that induced B-cell proliferation, immunoglobulin secretion, and anti-DNA antibody production. Unregulated cells of the AR-TC1 type could, therefore, lead to polyclonal B-cell activation and autoantibody production in vivo in the absence of exogenous antigenic stimulation.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"4 1","pages":"35-43"},"PeriodicalIF":0.0,"publicationDate":"1988-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13616828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Studies on recombination within the mouse H-2 complex: IV. Characterization of new recombinant haplotypes H-2t7, H-2t8, H-2as2, and H-2as3.","authors":"M Hauptfeld,&nbsp;V Hauptfeld,&nbsp;R Zeff,&nbsp;D C Shreffler","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Four new intra-H-2 recombinants were characterized serologically and functionally. In two of these recombinants, B10.ASR1 and B10.ASR7, crossing over occurred between the A alpha and E alpha subregions, very probably in E beta since most intra-I region recombinants thus far investigated at the DNA level appear to involve recombination within the E beta gene. In the other two recombinants, B10.ASR2 and B10.ARS8, crossing over occurred between the S and D subregions. B10.ASR2 and B10.ASR8, crossing over occurred between the S and D subregions. B10.ASR7, which is serologically indistinguishable from B10.BASR1 and B10.S(8R), slightly stimulates and strongly responds to both of these strains in MLR. The probable location of the B10.S(8R) stimulatory product is E beta. The H-2 composition of B10.ASR1 is closest to that of B10.S(9R) and B10.HTT; therefore, precise definition of the cross-over point at the DNA level will be of particular interest.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"4 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"1988-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14111388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epitopes on CD45R [T200] molecules define differentiation antigens on murine B and T lymphocytes.","authors":"M L Birkeland,&nbsp;J Metlay,&nbsp;V M Sanders,&nbsp;R Fernandez-Botran,&nbsp;E S Vitetta,&nbsp;R M Steinman,&nbsp;E Puré","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In the course of isolating hybridomas from rats that had been immunized with anti-Ig activated murine B lymphoblasts, we have identified three new mAb reactive with the T200 or leukocyte common antigen family (CD45). One, MB4B4, reacts with T200 on all leukocytes, and immunoprecipitates all the molecules that are recognized by an existing mAb to this family. Two others, MB23G2 and MB15C11, react with a subset of T200 molecules that has a unique tissue and cellular distribution. By FACS analysis and by immunocytochemical labeling of tissue sections, MB23G2/15C11 bind to most, if not all, small B and T lymphocytes, but react weakly with macrophages and dendritic cells. Expression of the MB23G2/15C11 T200 epitope exhibits four distinct features on lymphocytes: 1) activation of CD4+ cells in the mixed leukocyte reaction results in a decreased expression of MB23G2/15C11, on a subset of 30-60% of the T-cell blasts; 2) of 16 T-helper clones examined, clones of the TH2 phenotype express moderate to high levels of MB23G2/15C11 (2.5-19-fold increase in median fluorescence over control) while the TH1 clones express low to moderate levels (1.2-6.4-fold increase in median fluorescence over control) of the antigen recognized by these mAb; 3) The MB23G2/15C11 mAb do not react with germinal center cells in tissue sections of spleen, lymph node, and Peyer's patches; 4) MB23G2/15C11 reacts primarily with a subset of large thymocytes localized to the medulla. Therefore, MB23G2/15C11 define a subset-restricted form of T200 (CD45R) on murine lymphocytes. The tissue distribution of this T200 associated epitope is distinct from previously defined CD45 antigens and suggests a role during several pathways of lymphocyte development.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"4 2","pages":"71-85"},"PeriodicalIF":0.0,"publicationDate":"1988-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13621951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"Tolerization\" of human T-helper cell clones by chronic exposure to alloantigen: culture conditions dictate autocrine proliferative status but not acquisition of cytotoxic potential and suppressor-induction capacity.","authors":"G Pawelec,&nbsp;T Brocker,&nbsp;F W Busch,&nbsp;H J Bühring,&nbsp;N Fernandez,&nbsp;E M Schneider,&nbsp;P Wernet","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Induction of clonal anergy in T-helper (Th) cells may have a role in regulating immune responses. A model system for studying Th cell tolerization at the clonal level in vitro could be useful for investigating the mechanisms involved. Accordingly, alloreactive helper cells were maintained in culture with interleukin 2 (IL 2) by intermittent stimulation with specific antigen. Regardless of the frequency of antigen stimulation, clones of age less than ca. 35 population doublings (PD) were found to undergo antigen-specific autocrine clonal expansion in the absence of exogenous IL 2. Such young clones (designated as phase I) could therefore not be \"tolerized\" by frequent exposure to antigen. In contrast, most clones of age greater than ca. 35 PD could be tolerized by frequent exposure to antigen (designated as phase II clones). Their autocrine proliferation was then blocked, although they still recognized antigen specifically as shown by their retained ability to secrete interferon-gamma (IFN-gamma) and granulocyte-macrophage colony stimulating factor (GM-CSF). The mechanism of response failure involved both an inability to upregulate IL 2 receptors in the absence of exogenous IL 2, as well as an inability to secrete IL 2. These defects were not overcome by stimulation with mitogens or calcium ionophore and phorbol esther in place of alloantigen. T-cell receptor, alpha, beta, and gamma-chain gene rearrangements remained identical in phase I and phase II clones. Tolerization of phase II clones could be avoided by increasing the period between antigen exposures. Despite this, whether or not phase II cells were capable of autocrine proliferation, they were found to have acquired the novel function of inducing suppressive activity in fresh lymphocytes. Suppressor-induction was blocked by the broadly reactive MHC class II-specific monoclonal antibody (moAb) TU39, but not by moAb preferentially reacting only with HLA-DR, DQ, or DP. Sequential immunoprecipitation on T-cell clones showed the presence of a putative non-DR, DQ, DP, TU39+ molecule on phase II clones. However, this molecule was also found on phase I clones. The nature of the TU39-blockable suppressor-inducing determinant present on phase II but not on (most) phase I clones thus remains to be clarified. In addition to suppressor-induction activity, phase II clones also acquired lytic potential as measured in a lectin approximation system. Cytotoxic (CTX) potential was also not influenced by the frequency of antigenic stimulation and could be viewed as a constitutive modulation of clonal function.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"4 1","pages":"21-34"},"PeriodicalIF":0.0,"publicationDate":"1988-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14112254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The synergistic effects of anti-IgM and monoclonal anti-Ia antibodies in induction of murine B lymphocyte activation.","authors":"A R Baluyut,&nbsp;B Subbarao","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>MHC class II molecules on murine B lymphocytes have been shown to serve as recognition molecules in B cell-T cell interaction. The demonstration that a variety of B-cell stimuli such as anti-Ig, lipopolysaccharide, and interleukin-4 induce hyper-Ia expression has led to the proposal that Ia molecules may serve a role in B-cell activation. However, the question remains whether Ia molecules play a direct or indirect role in B-cell activation. In the present study it has been shown that Ia molecules may play a direct role in providing growth signals to B cells. Affinity purified monoclonal anti-Ia antibodies against both IA (MKD6) and IE (14.4.4) region encoded Ia molecules were able to enhance anti-mu induced B-cell proliferation in a synergistic manner. Anti-Ia antibodies alone had minimal effects on B-cell proliferation. Second, not all monoclonal anti-Ia antibodies, such as the anti-IA antibody 10.3.6.2, can induce this synergy. Third, the synergistic effects of anti-Ia on anti-mu activation can be demonstrated under serum-free culture conditions. Finally, the effects of anti-Ia antibodies on B-cell activation are not due to induction of interleukin-1 secretion in the cultures nor are due to interaction with the Fc receptors. Since such positive stimulatory effects of anti-Ia antibodies were not reported previously, rigorous steps were taken to demonstrate the reproducibility and specificity of the phenomenon. In over 20 experiments utilizing serum-free culture conditions, we have been able to consistently demonstrate that anti-Ia antibodies augmented anti-mu induced B-cell proliferation by 2.6 fold, on the average. In addition, the anti-Ia antibody induced augmentation of B-cell proliferation is also allele specific and does not require participation by T cells and adherent cells. All antibody preparations used in this study were also shown to be free of endotoxin as demonstrated by the Limulus Amebocyte Assay. The synergistic effects are specific to anti-Ia and anti-mu antibodies, since antibodies to Lyb2 failed to augment the response to anti-mu. The synergy between anti-Ia and anti-mu can be demonstrated with monoclonal (BET2) anti-mu or affinity purified goat anti-mu or (Fab)2 fragments of the anti-mu antibodies. These results suggest that B-cell surface Ia molecules may function as signal transducer molecules as well as recognition molecules which are important for B-cell activation.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"4 1","pages":"45-57"},"PeriodicalIF":0.0,"publicationDate":"1988-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14395239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha/beta heterodimeric T-cell receptor expression early in thymocyte differentiation.","authors":"M L Toribio,&nbsp;A de la Hera,&nbsp;J R Regueiro,&nbsp;C Márquez,&nbsp;M A Marcos,&nbsp;R Bragado,&nbsp;A Arnaiz-Villena,&nbsp;C Martínez","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The differentiation of T lymphocytes inside the thymus results in the acquisition of MHC-restricted specific functions mediated by clonally distributed alpha/beta heterodimeric T-cell receptors (TcR). Genes encoding the alpha and beta subunits of the clonotypic receptor (Ti) are rearranged during thymic ontogeny and expressed in association with the monomorphic CD3 complex. The regulation of the expression of functional TcR along T-cell development is thus crucial to establish the ontogenic events involved in the acquisition and selection of T-cell repertoires. Current views support that CD3-alpha/beta heterodimers are acquired late in ontogeny on developing thymocytes already expressing CD4 and/or CD8 surface molecules, whereas CD4- CD8- early precursors, representing the major population in the embryonic thymus, do not yet express the alpha/beta TcR. However, a novel CD3-associated gamma/delta heterodimer has been recently identified on the surface of this \"double negative\" subset both in thymocytes and in MHC-unrestricted peripheral T cells, suggesting that alpha/beta and gamma/delta heterodimeric receptors are independently expressed on the surface of distinct thymic subpopulations during T-cell development. In contrast to these results, we report here that a major proportion of CD3+1-4-8- adult human thymocytes, included within the early \"double negative\" subset, express alpha/beta heterodimeric receptors, as assessed by flow cytometric analysis using a frame-work monoclonal antibody (WT.31) against the alpha/beta TcR complex. These and previous data showing that CD3+1-4-8- \"double negative\" thymocytes constitute a functional intermediate ontogenic stage in the differentiation of CD3+1-4+8-/CD3+1-4-8+ mature T cells from CD3-1-4-8- early prothymocytes further support the relevance of the CD3+1-4-8- transitional subset as immediate intrathymic precursors of alpha/beta TcR-bearing mature T cells. Therefore, developmental regulation of alpha/beta TcR expression was analyzed at the DNA, RNA, and protein levels in those different thymic subpopulations, defined by both functional and phenotypic criteria. Our results demonstrate that multiple Ti beta gene rearrangements and beta RNA messages are already evident at the early prothymocyte stage. Moreover, expression of relative levels of both Ti alpha and Ti beta functional RNA transcripts, similar to those observed in mature thymic cells, were also present in CD3+1-4-8- thymocytes. According with these data, immunoprecipitation analysis using a specific anti-Ti alpha antisera revealed that both alpha and beta molecules are expressed on CD3+ \"double negative\" and mature thymocytes, but not in prothymocytes</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"3 6","pages":"347-62"},"PeriodicalIF":0.0,"publicationDate":"1988-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13991720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acquisition of repertoires of suppressor T cells under the influence of macrophages.","authors":"T Soejima,&nbsp;A Nagayama,&nbsp;T Sado,&nbsp;M Taniguchi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Acquisition of repertoires and genetic restriction specificities of suppressor T cells (Ts) and their factors were studied by using full allogeneic radiation bone marrow chimera and H-2 congenic pairs, B10.A(3R) and B10.A(5R), which received conventional or cloned macrophages by cell transfer. Suppressor T-cell factor (TsF) from C3H----C57BL/6 or C57BL/6----C3H chimera suppressed only donor but not host-type responses of either C3H or C57BL/6, in an antigen-specific fashion. However, if chimera mice were given conventional or cloned macrophages of the host type, the chimera TsF in turn suppressed both the responses of C3H and C57BL/6 mice but not those of the third party, BALB/c, indicating that macrophages are responsible for the acquisition of host restriction specificity. Similarly, B10.A(5R) mice developed I-Jb restricted Ts or TsF when the B10.A(3R) macrophage cell line was injected at the time of antigen priming. The reverse was also true. B10.A(3R) mice did generate I-Jk restricted Ts when they received the B10.A(5R) macrophage cell line. Thus, the results clearly demonstrated that B10.A(3R) or B10.A(5R) mice potentially possessed their ability to express both I-Jk and I-Jb determinants and that repertoires and genetic restriction specificity of Ts and their TsF were acquired at a macrophage level at the time of antigen-priming.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"4 2","pages":"87-95"},"PeriodicalIF":0.0,"publicationDate":"1988-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13993508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of B-cell differentiation: anti-mu antibodies have opposite effects on differentiation stimulated by bacterial lipopolysaccharide and 8-mercaptoguanosine.","authors":"L A Rollins-Smith,&nbsp;A R Lawton","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The mechanisms by which proliferation and differentiation are independently regulated are among the most interesting and complex problems in cell biology. Polyclonal activation of mouse B cells by bacterial lipopolysaccharide (LPS) has served as a useful model for study of these phenomena. Treatment of LPS-stimulated cells with high concentrations of bivalent antibodies to the IgM receptor uncouples these normally linked processes, enhancing proliferation while suppressing differentiation. A consensus summary of recent results from several laboratories suggests that modulation of the IgM receptor greatly reduces mRNA levels for mu and k chains, primarily by blocking the increased rate of transcription usually triggered by LPS. The expression of other differentiation-linked proteins, for example J chain and endogenous retroviral proteins, is similarly downregulated. Basal transcription of the mu-delta complex and other constitutively expressed genes, such as Class I and Class II MHC genes, is not affected. Both suppression of differentiation and enhancement of proliferation in this system depend upon the simultaneous presence of anti-mu and LPS--cells treated with saturating concentrations of anti-mu, washed, and then cultured in LPS are not suppressed, while cells pulsed briefly with both agents before culture with LPS are suppressed. These observations have led us to examine interactions of anti-mu antibody with another potent polyclonal B cell activator, 8-mercaptoguanosine (8SGuo). In this report, we show that anti-mu antibodies have polar effects on B-cell differentiation induced by 8SGuo and LPS. Differentiation induced by the former is strongly enhanced, while that induced by the latter is suppressed. The signal induced by co-stimulation with LPS and anti-mu is dominant, as suppression occurs when LPS is added to cells stimulated with 8SGuo and anti-mu at initiation or as late as 48 hours of a 96-hour culture. We present preliminary evidence that augmented B-cell differentiation caused by combined stimulation with 8SGuo and anti-mu is dependent upon a soluble factor released during the first 24 hours of culture. These results provide additional evidence that suppression of LPS-driven B-cell differentiation is an active process, probably mediated by a trans-acting repressor of transcription. The mechanisms by which 8SGuo and anti-mu interact to enhance B-cell differentiation remain to be determined.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"4 1","pages":"9-19"},"PeriodicalIF":0.0,"publicationDate":"1988-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14395240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}