scholarly journals MicroRNA-155 is essential for the optimal proliferation and survival of plasmablast B cells

2019 ◽  
Vol 2 (3) ◽  
pp. e201800244 ◽  
Author(s):  
Giuseppina Arbore ◽  
Tom Henley ◽  
Laura Biggins ◽  
Simon Andrews ◽  
Elena Vigorito ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Comparative Analysis ◽  
T Cell ◽  
B Cells ◽  
Antibody Response ◽  
Antibody Production ◽  
Metabolic Process ◽  
Cellular Processes ◽  
T Cell Help

A fast antibody response can be critical to contain rapidly dividing pathogens. This can be achieved by the expansion of antigen-specific B cells in response to T-cell help followed by differentiation into plasmablasts. MicroRNA-155 (miR-155) is required for optimal T-cell–dependent extrafollicular responses via regulation of PU.1, although the cellular processes underlying this defect are largely unknown. Here, we show that miR-155 regulates the early expansion of B-blasts and later on the survival and proliferation of plasmablasts in a B-cell–intrinsic manner, by tracking antigen-specific B cells in vivo since the onset of antigen stimulation. In agreement, comparative analysis of the transcriptome of miR-155–sufficient and miR-155–deficient plasmablasts at the peak of the response showed that the main processes regulated by miR-155 were DNA metabolic process, DNA replication, and cell cycle. Thus, miR-155 controls the extent of the extrafollicular response by regulating the survival and proliferation of B-blasts, plasmablasts and, consequently, antibody production.

scholarly journals Autoreactive marginal zone B cells are spontaneously activated but lymph node B cells require T cell help

2006 ◽  
Vol 203 (8) ◽  
pp. 1985-1998 ◽  
Author(s):  
Laura Mandik-Nayak ◽  
Jennifer Racz ◽  
Barry P. Sleckman ◽  
Paul M. Allen
Keyword(s):  
Lymph Node ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Marginal Zone ◽  
B Cell Tolerance ◽  
Marginal Zone B Cells ◽  
T Cell Help

In K/BxN mice, arthritis is induced by autoantibodies against glucose-6-phosphate-isomerase (GPI). To investigate B cell tolerance to GPI in nonautoimmune mice, we increased the GPI-reactive B cell frequency using a low affinity anti-GPI H chain transgene. Surprisingly, anti-GPI B cells were not tolerant to this ubiquitously expressed and circulating autoantigen. Instead, they were found in two functionally distinct compartments: an activated population in the splenic marginal zone (MZ) and an antigenically ignorant one in the recirculating follicular/lymph node (LN) pool. This difference in activation was due to increased autoantigen availability in the MZ. Importantly, the LN anti-GPI B cells remained functionally competent and could be induced to secrete autoantibodies in response to cognate T cell help in vitro and in vivo. Therefore, our study of low affinity autoreactive B cells reveals two distinct but potentially concurrent mechanisms for their activation, of which one is T cell dependent and the other is T cell independent.

scholarly journals T cell help controls the speed of the cell cycle in germinal center B cells

Science ◽  
2015 ◽  
Vol 349 (6248) ◽  
pp. 643-646 ◽  
Author(s):  
A. D. Gitlin ◽  
C. T. Mayer ◽  
T. Y. Oliveira ◽  
Z. Shulman ◽  
M. J. K. Jones ◽  
...  
Keyword(s):  
Cell Cycle ◽  
T Cell ◽  
B Cells ◽  
Germinal Center ◽  
T Cell Help ◽  
Germinal Center B Cells

scholarly journals Differential requirement for OBF-1 during antibody-secreting cell differentiation

2005 ◽  
Vol 201 (9) ◽  
pp. 1385-1396 ◽  
Author(s):  
Lynn M. Corcoran ◽  
Jhagvaral Hasbold ◽  
Wendy Dietrich ◽  
Edwin Hawkins ◽  
Axel Kallies ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Antibody Production ◽  
Transcriptional Coactivator ◽  
Secreting Cell ◽  
Antibody Secreting Cell ◽  
Analytical System ◽  
Induce Antibody

Resting B cells can be cultured to induce antibody-secreting cell (ASC) differentiation in vitro. A quantitative analysis of cell behavior during such a culture allows the influences of different stimuli and gene products to be measured. The application of this analytical system revealed that the OBF-1 transcriptional coactivator, whose loss impairs antibody production in vivo, has two effects on ASC development. Although OBF-1 represses early T cell–dependent (TD) differentiation, it is also critical for the completion of the final stages of ASC development. Under these conditions, the loss of OBF-1 blocks the genetic program of ASC differentiation so that Blimp-1/prdm1 induction fails, and bcl-6, Pax5, and AID are not repressed as in control ASC. Retroviral complementation confirmed that OBF-1 was the critical entity. Surprisingly, when cells were cultured in lipopolysaccharide to mimic T cell–independent conditions, OBF-1–null B cells differentiated normally to ASC. In the OBF-1−/− ASC generated under either culture regimen, antibody production was normal or only modestly reduced, revealing that Ig genes are not directly dependent on OBF-1 for their expression. The differential requirement for OBF-1 in TD ASC generation was confirmed in vivo. These studies define a new regulatory role for OBF-1 in determining the cell-autonomous capacity of B cells to undergo terminal differentiation in response to different immunological signals.

scholarly journals ROLE OF COMPLEMENT IN INDUCTION OF ANTIBODY PRODUCTION IN VIVO

1974 ◽  
Vol 140 (1) ◽  
pp. 126-145 ◽  
Author(s):  
M. B. Pepys
Keyword(s):  
B Cells ◽  
Antibody Response ◽  
B Cell ◽  
Antibody Production ◽  
Antibody Responses ◽  
Cobra Venom ◽  
Sheep Erythrocytes ◽  
C3 Receptors

In an in vivo study in mice, suppression by the C3-cleaving protein of cobra venom (CoF), and other C3-reactive agents (zymosan, aggregated IgG, anti-C3 antibodies, and type III pneumococcal polysaccharide) of the thymus-dependent antibody responses to sheep erythrocytes, ovalbumin, and human IgG was demonstrated. The thymus-independent antibody response to polyvinyl-pyrrolidone was however unaffected by CoF. These and other published observations suggest that there may be a requirement for functional C3 in induction of thymus-dependent but not thymus-independent antibody production. A model for the role of C3 in lymphocyte cooperation is proposed based on these data analyzed in the light of existing knowledge of this process. It is postulated that fixed C3 interacting with macrophage See PDF for Structure and B-cell C3 receptors might enhance or facilitate T-dependent presentation of antigen to B cells.

scholarly journals Establishment of an inbred line of mice that express a synergistic immune defect precluding in vitro responses to type 1 and type 2 antigens, B cell mitogens, and a number of T cell-derived helper factors.

1983 ◽  
Vol 158 (5) ◽  
pp. 1401-1414 ◽  
Author(s):  
J J Mond ◽  
G Norton ◽  
W E Paul ◽  
I Scher ◽  
F D Finkelman ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
C3h Mice ◽  
Immune Defect ◽  
T Cell Help

Introduction of the CBA/N X-linked gene into C3H mice has resulted in the establishment of a new strain of mice that has profound immunologic defects. B cells from these mice show significantly impaired in vitro immune responses to the T cell-independent type 1 antigen trinitrophenyl-Brucella abortus (TNP-BA) as well as markedly reduced proliferative responses to a number of B cell mitogens when compared with the responses of the parental control mice. The in vivo response of such mice to TNP-BA is, however, comparable to that of CBA/N mice. Furthermore, B cells from C3.CBA/N mice are unresponsive to the plaque-forming cell enhancing effects induced by EL4-derived supernatant in the presence of TNP-BA, unlike B cells obtained from CBA/N or C3H/Hen mice whose responsiveness to TNP-BA can be significantly enhanced in the presence of EL4-derived supernatant. The model we have presented to best explain these results suggests that B cells from C3.CBA/N mice can be stimulated only under conditions in which they can interact with carrier-specific T cell help and not under conditions where factor-dependent responses are dominant.

scholarly journals Cross-linking of membrane immunoglobulin D, in the absence of T cell help, kills mature B cells in vivo.

1995 ◽  
Vol 181 (2) ◽  
pp. 515-525 ◽  
Author(s):  
F D Finkelman ◽  
J M Holmes ◽  
O I Dukhanina ◽  
S C Morris
Keyword(s):  
Cell Death ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Number ◽  
Cross Linking ◽  
Membrane Immunoglobulin ◽  
Cross Links ◽  
T Cell Help

In vivo experiments were performed to determine whether the cross-linking of membrane immunoglobulin (mIg) D on mature B cells, in the absence of T cell help, leads to B cell death. Mice were injected with either a monoclonal antibody (mAb) that cross-links mIgD effectively or a mAb that binds to mIgD avidly but cross-links it to a limited extent, and effects on B cell number and B cell Ia, mIgM, and mIgD expression were observed. In most experiments, mice were pretreated with anti-interleukin 7 mAb to prevent the generation of new bone marrow B cells, and with anti-CD4 mAb to prevent the generation of T cell help. In some experiments, mice also received anti-Fc gamma RII mAb to prevent cross-linking of mIgD with Fc gamma RII, and cobra venom factor to prevent possible mIg-complement receptor interactions and complement-mediated killing of B cells. The results of these studies demonstrate that (a) even limited cross-linking of mIgD on mature B cells can lead to B cell death; (b) increased cross-linking of mIgD leads to increased B cell death; (c) the loss of B cells is first detected 2 d after anti-IgD mAb injection and increases during the subsequent 3 d; (d) sustained modulation of mIgD may be necessary to cause B cell death; (e) mIgMdull but not mIgMbright B cells are lost in mice injected with anti-IgD mAbs; and (f) T cell help prevents or minimizes B cell death.

scholarly journals Mice transgenic for a soluble form of murine CTLA-4 show enhanced expansion of antigen-specific CD4+ T cells and defective antibody production in vivo.

1994 ◽  
Vol 179 (3) ◽  
pp. 809-817 ◽  
Author(s):  
F Ronchese ◽  
B Hausmann ◽  
S Hubele ◽  
P Lane
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Transgenic Mice ◽  
T Cell Activation ◽  
Antibody Production ◽  
T Cell Responses ◽  
Soluble Form ◽  
Cell Responses

CD4+ T cell responses were analyzed in transgenic mice expressing a soluble form of murine CTLA-4, mCTLA4-H gamma 1, which blocks the interaction of the T cell activation molecules CD28 and CTLA-4 with their costimulatory ligands. Consistent with previous reports (Linsley, P. S., P. M. Wallace, J. Johnson, M. G. Gibson, J. L. Greene, J. A. Ledbetter, C. Singh, and M. A. Tepper. 1992. Science (Wash. DC). 257:792), T cell-dependent antibody production was profoundly inhibited in mCTLA4-H gamma 1 transgenic mice immunized with a protein antigen. Surprisingly, however, transgenic mice could generate quantitatively and qualitatively normal primary T cell responses, as measured by limiting dilution assays and lymphokine production. In addition, in vivo expansion of antigen-specific T cells after secondary or tertiary immunization was enhanced in mCTLA4-H gamma 1 transgenics as compared with normal mice. Although unable to deliver cognate help to B cells in vivo, T cells from mCTLA4-H gamma 1 transgenic mice were not anergic as they could help B cells to produce specific antibodies when adoptively transferred into nude hosts. Taken together, these data suggest that the engagement of CD28 and/or CTLA-4 may not be required for the induction of T cell responses, as is currently understood, but rather for the expression of T cell effector function such as the delivery of T cell help to B cells.

scholarly journals Effects of blocking helper T cell induction in vivo with anti-Ia antibodies. Possible role of I-A/E hybrid molecules as restriction elements.

1980 ◽  
Vol 152 (4) ◽  
pp. 996-1010 ◽  
Author(s):  
J Sprent
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Activated T Cells ◽  
Hybrid Molecules ◽  
T Cell Help

To examine the role of Ia antigens in controlling T cell activation in vivo, unprimed (CBA X B6)F1 (H-2k X H-2b) T cells were positively selected to sheep erythrocytes (SRC) for 5 d in irradiated F1 mice in the presence of large doses of anti-Iak antibody. With selection in the presence of broad-spectrum anti-Iak antibody (A.TH anti-A.TL antiserum), the activated T cells were markedly reduced in their capacity to collaborate with either B10.BR (I-Ak I-Bk I-Jk I-Ek I-Ck) (kkkkk) or B10.A(4R) (kbbbb) B cells but gave good helper responses with B10 (bbbbb) and (B10 X B10.BR)F1 B cells. Because there was no evidence for suppression, these findings were taken to imply that the anti-Iak antibody bound to Ia determinants on radioresistant macrophagelike cells of F1 host origin and blocked the activation of the IGk-restricted subgroup of F1 T cells but did not affect activation of the Iab-restricted T cell subgroup. Analogous experiments in which F1 T cells were selected to SRC in F1 mice in the presence of monoclonal anti-I-Ak antibody gave different results. In this situation, the reduction in T cell help for Iak-bearing B cells applied to B10.A(4R) B cells but not to B10.BR B cells. With selection of F1 T cells in B10.A(4R) mice, by contrast, anti-I-Ak antibody blocked T cell help for both B10.A(4R) and B10.BR B cells. These data suggested that genes telomeric to the I-A subregion were involved in controlling T cell activation and T-B collaboration. Because no evidence could be found that I-B through I-C determinants per se could act as restrictions elements, the working hypothesis for the data is that Iak-restricted T cells consist of two subgroups of cells: one subgroup is restricted by I-A-encoded molecules, whereas the other is restricted by I-A/E hybrid molecules encoded by two separated genes situated in the I-A and I-E subregions, respectively. The notion that A/E hybrid molecules serve as restriction elements is in line with the findings of other workers that these molecules can act as alloantigens and control responses to certain antigens under double Ir gene control.

scholarly journals A brief history of T cell help to B cells

2015 ◽  
Vol 15 (3) ◽  
pp. 185-189 ◽  
Author(s):  
Shane Crotty
Keyword(s):  
T Cell ◽  
B Cells ◽  
History Of ◽  
T Cell Help

scholarly journals Cd40-Independent Pathways of T Cell Help for Priming of Cd8+ Cytotoxic T Lymphocytes

2000 ◽  
Vol 191 (3) ◽  
pp. 541-550 ◽  
Author(s):  
Zhengbin Lu ◽  
Lingxian Yuan ◽  
Xianzheng Zhou ◽  
Eduardo Sotomayor ◽  
Hyam I. Levitsky ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Cell Communication ◽  
Cd8 T Cell ◽  
Cd4 Help ◽  
T Cell Help

In many cases, induction of CD8+ CTL responses requires CD4+ T cell help. Recently, it has been shown that a dominant pathway of CD4+ help is via antigen-presenting cell (APC) activation through engagement of CD40 by CD40 ligand on CD4+ T cells. To further study this three cell interaction, we established an in vitro system using dendritic cells (DCs) as APCs and influenza hemagglutinin (HA) class I and II peptide–specific T cell antigen receptor transgenic T cells as cytotoxic T lymphocyte precursors and CD4+ T helper cells, respectively. We found that CD4+ T cells can provide potent help for DCs to activate CD8+ T cells when antigen is provided in the form of either cell lysate, recombinant protein, or synthetic peptides. Surprisingly, this help is completely independent of CD40. Moreover, CD40-independent CD4+ help can be documented in vivo. Finally, we show that CD40-independent T cell help is delivered through both sensitization of DCs and direct CD4+–CD8+ T cell communication via lymphokines. Therefore, we conclude that CD4+ help comprises at least three components: CD40-dependent DC sensitization, CD40-independent DC sensitization, and direct lymphokine-dependent CD4+–CD8+ T cell communication.

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