scholarly journals Accessibility of the promoter sequence in the J-chain gene is regulated by chromatin changes during B-cell differentiation.

1986 ◽  
Vol 6 (11) ◽  
pp. 4031-4038 ◽  
Author(s):  
M E Minie ◽  
M E Koshland
Keyword(s):  
B Cell ◽  
Early Stage ◽  
Promoter Sequence ◽  
Immunoglobulin M ◽  
Chain Gene ◽  
B Cell Differentiation ◽  
Cell Stage ◽  
J Chain ◽  
Lymphoid Lines ◽  
Nuclease Digestion

The gene for the immunoglobulin M (IgM)-polymerizing protein, the J chain, is activated when the mature B cell is triggered to secrete pentamer IgM. Activation of the gene was found to be associated with chromatin changes in a 240-base-pair region at the 5' end of the gene. Analyses of lymphoid lines showed that the 5' region was resistant to nuclease digestion at the immature B-cell stage; it became slightly more accessible in mature B cells and cells at an early stage in the IgM response and then displayed an open, hypersensitive structure in IgM-secreting cells. In addition, analyses of normal, mitogen-stimulated lymphocytes showed that the open hypersensitive structure was coinducible with J-chain gene expression. These results suggest that the 5' chromatin changes precede transcription, making control sequences within the site accessible to regulatory factors.

Accessibility of the promoter sequence in the J-chain gene is regulated by chromatin changes during B-cell differentiation

1986 ◽  
Vol 6 (11) ◽  
pp. 4031-4038
Author(s):  
M E Minie ◽  
M E Koshland
Keyword(s):  
B Cell ◽  
Early Stage ◽  
Promoter Sequence ◽  
Immunoglobulin M ◽  
Chain Gene ◽  
B Cell Differentiation ◽  
Cell Stage ◽  
J Chain ◽  
Lymphoid Lines ◽  
Nuclease Digestion

The gene for the immunoglobulin M (IgM)-polymerizing protein, the J chain, is activated when the mature B cell is triggered to secrete pentamer IgM. Activation of the gene was found to be associated with chromatin changes in a 240-base-pair region at the 5' end of the gene. Analyses of lymphoid lines showed that the 5' region was resistant to nuclease digestion at the immature B-cell stage; it became slightly more accessible in mature B cells and cells at an early stage in the IgM response and then displayed an open, hypersensitive structure in IgM-secreting cells. In addition, analyses of normal, mitogen-stimulated lymphocytes showed that the open hypersensitive structure was coinducible with J-chain gene expression. These results suggest that the 5' chromatin changes precede transcription, making control sequences within the site accessible to regulatory factors.

scholarly journals Ras Mediates Effector Pathways Responsible for Pre-B Cell Survival, Which Is Essential for the Developmental Progression to the Late Pre-B Cell Stage

2000 ◽  
Vol 192 (2) ◽  
pp. 171-182 ◽  
Author(s):  
Hitoshi Nagaoka ◽  
Yoshimasa Takahashi ◽  
Reiko Hayashi ◽  
Tohru Nakamura ◽  
Kumiko Ishii ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Survival ◽  
Chain Gene ◽  
B Cell Differentiation ◽  
Antigen Receptors ◽  
Cell Stage ◽  
Light Chain Gene ◽  
B Cell Survival ◽  
Effector Pathways

Ras is essential for the transition from early B cell precursors to the pro-B stage, and is considered to be involved in the signal cascade mediated by pre-B cell antigen receptors. To examine the role of p21ras in the late stage of B cell differentiation, we established transgenic mice (TG) expressing a dominant-inhibitory mutant of Ha-ras (Asn-17 Ha-ras) in B lineage cells at high levels after the early B cell precursor stage. Expression of p21Asn-17 Ha-ras was associated with a prominent reduction in the number of late pre-B cells, but had little effect on proliferation of early pre-B cells. Inhibition of p21ras activity markedly reduced the life span of pre-B cells, due, at least in part, to downregulation of the expression of an antiapoptotic protein, Bcl-xL. Thus, the apparent role for p21ras activity in pre-B cell survival may explain the decreased numbers of late pre-B cells in Asn-17 Ha-ras TG. Consistent with this possibility, overexpression of Bcl-2 in Asn-17 Ha-ras TG reversed the reduction in the number of late pre-B cells undergoing immunoglobulin light chain gene (IgL) rearrangement and progressing to immature B cells. These results suggest that p21ras mediates effector pathways responsible for pre-B cell survival, which is essential for progression to the late pre-B and immature B stages.

scholarly journals A Stage-Specific Enhancer of Immunoglobulin J Chain Gene Is Induced by Interleukin-2 in a Presecretor B Cell Stage

Immunity ◽  
1998 ◽  
Vol 8 (3) ◽  
pp. 285-295 ◽  
Author(s):  
Chang-Joong Kang ◽  
Colleen Sheridan ◽  
Marian Elliott Koshland
Keyword(s):  
B Cell ◽  
Interleukin 2 ◽  
Chain Gene ◽  
Cell Stage ◽  
J Chain

scholarly journals Extended Duration of DH–JH Rearrangement in Immunoglobulin Heavy Chain Transgenic Mice: Implications for Regulation of Allelic Exclusion

1999 ◽  
Vol 189 (8) ◽  
pp. 1295-1305 ◽  
Author(s):  
Yung Chang ◽  
Melvin J. Bosma ◽  
Gayle C. Bosma
Keyword(s):  
B Cell ◽  
Extended Period ◽  
Chain Gene ◽  
Allelic Exclusion ◽  
B Cell Differentiation ◽  
Cell Stage ◽  
Normal Representation ◽  
Chain Gene Rearrangement ◽  
Extended Duration ◽  
B Lineage

Here we show that suppression of VH–DJH rearrangement in mice bearing a μ heavy (H) chain transgene (μ-tg mice) is associated with an extended period of DH–JH rearrangement, the first step of Immunoglobulin H chain gene rearrangement. Whereas DH–JH rearrangement is normally initiated and completed at the pro-B cell stage, in μ-tg mice it continues beyond this stage and occurs most frequently at the small (late) pre-B stage. Despite ongoing DH–JH rearrangement in late pre-B cells of μ-tg mice, VH–DJH rearrangement is not detectable in these cells. We infer that the lack of VH–DJH rearrangement primarily reflects tg-induced acceleration of B cell differentiation past the stage at which rearrangement of VH elements is permissible. In support of this inference, we find that the normal representation of early B lineage subsets is markedly altered in μ-tg mice. We suggest that the effect of a productive VH–DJH rearrangement at an endogenous H chain allele may be similar to that of a μ-tg; i.e., cells that make a productive VH–DJH rearrangement on the first attempt rapidly progress to a developmental stage that precludes VH–DJH rearrangement at the other allele (allelic exclusion).

Constitutive Lymphoid Expression of the Nuclear Form of RNase H1 Is Associated with a Developmental Bottleneck at the Pro-B Cell Stage of B Cell Differentiation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4702-4702
Author(s):  
Lina A. Gugliotti ◽  
Kiran B. Sakhuja ◽  
Hongsheng Wang ◽  
Julia Pinkhasov ◽  
Paul E. Love ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Dna Sequences ◽  
Conflicts Of Interest ◽  
Cell Receptor ◽  
Chain Gene ◽  
B Cell Differentiation ◽  
Loop Formation ◽  
Dna Breaks ◽  
Cell Stage

Abstract Abstract 4702 The development of B lymphocytes and the process of lineage determination are initiated by expression of a set of transcriptional regulators leading to V(D)J recombination events initiated by double-strand DNA breaks. Subsequently, these recombinations form DNAs that permit transcription of immunoglobulin genes and translation of the corresponding mRNAs, first by joining the V(D)J DNA sequences, then by recombination, that generates various isotypes of immunoglobulins by class-switch recombination (CSR). Formation of R-loops, regions containing RNA/DNA hybrid and a displaced single-stranded DNA, have been shown to lead to recombination in bacteria, yeast, HeLa and chick cells. Expression in each of these cases of excess ribonuclease H1 (RNase H1), a class of enzymes that degrade RNA in RNA/DNA hybrids, has ameliorated the deleterious effects and decreased recombinational events associated with R-loop formation. R-loops have been observed following transcription of the switch regions that occurs during CSR. The possibility that R-loops are important in V(D)J recombination has not been addressed, and whether ribonucleases H (RNases H) play a role in this process is still uncertain. Transgenic (TG) mice that overexpress RNase H1 in B and T cells (M27F7) were employed in this study. FACS analysis of hematopoietic cells from TG mice revealed a decrease in pre-B cells in the bone marrow. The data indicate a block at the pro-B to pre-B stage of B cell development, which may be the result of apoptosis due to the failure to generate a productive VH-D-JH rearrangement and expression of the pre-B cell receptor. A few B cells that successfully passed these checkpoints predominately differentiated into marginal zone and B1a cells in the peripheral lymphoid organs of the TG mice. These data suggest that R-loops are important in H chain gene rearrangement. This research is supported by the Intramural Research Program of the National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Allergy and Infectious Diseases. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Changes in J chain and mu chain RNA expression as a function of B cell differentiation.

1984 ◽  
Vol 160 (3) ◽  
pp. 877-892 ◽  
Author(s):  
G Lamson ◽  
M E Koshland
Keyword(s):  
B Cell ◽  
Time Course ◽  
Rna Synthesis ◽  
Rna Expression ◽  
B Cell Differentiation ◽  
Activated Lymphocytes ◽  
J Chain ◽  
Pattern Characteristic ◽  
Kinetics Of ◽  
Lymphoid Cell Lines

The time course of differentiative events in the pentamer IgM response was examined by following the expression of J chain and mu chain RNA and their protein products in mitogen-stimulated lymphocytes. The analyses showed that the shift to mus RNA synthesis begins shortly after stimulation and precedes proliferation of the cells and any increase in mu RNA levels. In contrast, expression of J chain RNA and the amplification of J chain and mus message are late events that coincide with a phase of rapid proliferation and with the secretion of pentamer IgM antibody. The kinetics of J and mu chain RNA expression observed in normal lymphocytes were supported by analyses of lymphoid cell lines. B lymphomas were found to display the RNA pattern characteristic of early-activated lymphocytes, i.e., a partial shift to mus RNA production and no J chain RNA, whereas IgM-secreting lines resembled late-activated lymphocytes in their expression of high levels of both mus and J chain mRNA. Moreover, the kinetics of J and mus chain RNA expression correlates with the sequential action of B cell lymphokines in the induction of the pentamer IgM response. This correlation suggests that the successive differentiative changes are triggered by successive membrane stimuli.

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