Three restriction points in the cell cycle of activated murine B lymphocytes.

Melchers, Fritz; Lernhardt, Waldemar

doi:10.1073/pnas.82.22.7681

Cited by 61 publications

(27 citation statements)

References 34 publications

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“…Recent studies have confirmed a need for monocyte-and T cell-derived factors in maintaining the replicative cycle of murine B cells which are already proliferating. Here, the details appear somewhat different with monocyte factors acting early in GI while T cell products are required in the G2 phase of the cell cycle [27]. Present understanding of the factors influencing human B cell growth and proliferation is less clear.…”

Section: Discussionmentioning

confidence: 95%

Ligation of the CD23, p45 (BLAST‐2, EBVCS) antigen triggers the cell‐cycle progression of activated B lymphocytes

et al. 1986

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CD23,p45 (BLAST-2,EBVCS) is a 45-kDa lineage-restricted antigen which appears on the surface of human B cells shortly after activation. A monoclonal antibody (MHM6) to CD23,p45, as well as a polyclonal rabbit antibody raised against the purified antigen were found to promote DNA synthesis in purified tonsillar B cells which had been activated with phorbol ester. Interleukin 1, which was not, by itself, stimulatory for either resting or activated B cells, significantly augmented the growth-promoting properties of MHM6. Kinetic studies indicated that while MHM6 exerted its influence in early G1, interleukin 1 acted later in the cycle just prior to the entry of cells into S phase. The findings demonstrate a role for CD23,p45 in triggering the progression of activated B lymphocytes through the G1 phase of the cell cycle. The possibility that this antigen serves as a receptor for a B cell stimulatory factor is discussed.

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Section: Discussionmentioning

confidence: 95%

Ligation of the CD23, p45 (BLAST‐2, EBVCS) antigen triggers the cell‐cycle progression of activated B lymphocytes

et al. 1986

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“…LMP appears to be synthesized at or around the time cells start to synthesize DNA (S) and its expression appears to be essential for immortalization (Walls et al, 1989; and with T. Azim, unpublished observations). The roles of EBNA 3, 4, 5 and 6 have not yet been determined but their temporal expression in cells becoming immortalized suggests that functions associated with progression through the cell cycle including the transition from G2 to M (Melchers & Lernhardt, 1985;Gordon & Guy, 1987) should be considered (see Fig. 7).…”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr Virus Latent Gene Expression during the Initiation of B Cell Immortalization

Allday¹,

Crawford²,

Griffin³

1989

Journal of General Virology

119

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SUMMARYEpstein-Barr virus (EBV) has the capacity to immortalize a subpopulation of resting B lymphocytes. Lymphoblastoid cell lines (LCL) established in this way carry the latent EBV genome as multiple copies of an extrachromasomal episome. Viral gene expression in LCLs is highly restricted; products identified correspond to a membrane protein (latent membrane protein; LMP), a nuclear antigen complex (Epstein-Barr nuclear antigens; EBNAs 1 to 6), two small RNA species (EBERs 1 and 2) and RNA species thought to encode a second membrane-associated polypeptide designated terminal protein (TP). Here we have investigated the temporal sequence of expression of the characterized 'latent' proteins during the initiation of immortalization when resting B cells are stimulated to enter and traverse the cell cycle. The analysis has been carried out on prolymphocytic leukaemia cells infected in vitro with either the immortalizing B95-8 strain of virus or the non-immortalizing P3HR1 strain. The results reveal that following B95-8 infection, a sequence of EBV expression is initiated within approximately 8 h with the synthesis of detectable levels of EBNA 2 shortly followed by EBNAs 1, 3, 4, 5 and 6. There is then a delay of approximately 40 h until the expression of LMP completes the latent pattern of proteins found in LCLs. P3HR1 infection, however, produces only transient expression of some EBNA species in a small percentage of cells after approximately 48 h. These observations suggest the failure of P3HR1 virus to immortalize may not be due solely to the absence of EBNA 2 expression and that cellular and/or virus-mediated events occur after EBNA synthesis which then facilitate efficient LMP expression and immortalization.

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“…The signals involved in activating B cells from a quiescent state to enter the G, phase of the cell cycle appear to be separable from those required for activated cells to progress through G, phase into S phase (7,24,26,30). Binding of surface immunoglobulin, the antigenspecific receptor on B cells, by antibodies to immunoglobulin activates resting B cells.…”

mentioning

confidence: 99%

Two-step stimulation of B lymphocytes to enter DNA synthesis: synergy between anti-immunoglobulin antibody and cytochalasin on expression of c-myc and a G1-specific gene.

Buckler¹,

Rothstein²,

Sonenshein³

1988

Mol. Cell. Biol.

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Previously we demonstrated that stimulation of resting murine splenic B lymphocytes with goat anti-mouse immunoglobulin antibody (GaMIg) plus cytochalasin D (CD) led to DNA synthesis; GaMIg and CD added simultaneously, or GaMIg added before CD, induced this response (T. L. Rothstein, J. Immunol. 136:813-816, 1986). Cells similarly treated with GaMIg or CD alone did not enter S phase. Here we have measured the effects of this two-signal stimulation on the c-myc, 2F1, and y-actin genes. The expression of these growth-related genes is known to change either during the Go-to-G, transition or in the G1 phase of the cell cycle. For the 2F1 and c-myc genes, neither the GaMIg nor CD stimulus alone led to a prolonged increase in mRNA levels, whereas GaMIg plus CD allowed for continuous elevated expression of these genes. Furthermore, GaMIg pretreatment rendered expression of the c-myc and 2F1 genes susceptible to subsequent action by CD. In contrast, CD alone was sufficient to produce changes in -y-actin gene expression. Thus there are synergistic effects of competence-and progressionlike factors on the expression of the c-myc and 2F1 genes, and these effects correlate with the progression of B lymphocytes to DNA synthesis.Stimulation of resting B lymphocytes to proliferate involves at least two steps. The signals involved in activating B cells from a quiescent state to enter the G, phase of the cell cycle appear to be separable from those required for activated cells to progress through G, phase into S phase (7,24,26,30). Binding of surface immunoglobulin, the antigenspecific receptor on B cells, by antibodies to immunoglobulin activates resting B cells. This is thought to represent a model for the cross-linking of surface immunoglobulin by polyvalent antigen. B cells activated with modest doses of anti-immunoglobulin are induced to enlarge (29), to increase RNA synthesis (29), and to increase expression of surface Ia molecules (28), but DNA synthesis does not occur. Progression from the activated state to S phase requires the presence of B-cell growth factor(s) (14,18,25). Although the requirements for both anti-immunoglobulin and B-cell growth factor(s) have been demonstrated, the mechanisms of action of these stimuli have not been elucidated.Recent work from one of these laboratories has demonstrated that any one of a number of cytochalasins in combination with modest doses of goat anti-mouse immunoglobulin (GaMIg) induces murine splenic B cells to initiate DNA replication (33). Cytochalasins are a family of fungal metabolites which have various effects on cell architecture and metabolism. Interestingly, all of the cytochalasins which costimulate B cells bind to actin and inhibit actin filament elongation (9,20,33). Further investigation of this model system indicated that GaMIg and cytochalasin act sequentially, in that cytochalasin stimulates DNA synthesis in . In contrast, preincubation of cells with cytochalasin D (CD) for any length of time did not lead to DNA synthesis when such cells were subsequently washed ...

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Three restriction points in the cell cycle of activated murine B lymphocytes.

Cited by 61 publications

References 34 publications

Ligation of the CD23, p45 (BLAST‐2, EBVCS) antigen triggers the cell‐cycle progression of activated B lymphocytes

Ligation of the CD23, p45 (BLAST‐2, EBVCS) antigen triggers the cell‐cycle progression of activated B lymphocytes

Epstein-Barr Virus Latent Gene Expression during the Initiation of B Cell Immortalization

Two-step stimulation of B lymphocytes to enter DNA synthesis: synergy between anti-immunoglobulin antibody and cytochalasin on expression of c-myc and a G1-specific gene.

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