scholarly journals The fate of self-reactive B cells depends primarily on the degree of antigen receptor engagement and availability of T cell help.

1996 ◽  
Vol 183 (5) ◽  
pp. 2313-2328 ◽  
Author(s):  
D A Fulcher ◽  
A B Lyons ◽  
S L Korn ◽  
M C Cook ◽  
C Koleda ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Life Span ◽  
Cell Tracking ◽  
Soluble Form ◽  
Critical Threshold ◽  
Short Life ◽  
Short Life Span ◽  
T Cell Help ◽  
Self Antigen

Self-reactive B cells from tolerant double-transgenic (Dbl-Tg) mice coexpressing hen egg lysozyme (HEL) and rearranged anti-HEL immunoglobulin genes have a relatively short life span when compared to normal B cells, irrespective of whether they are exposed to antigen in multivalent membrane-bound form (mHEL-Dbl-Tg mice) or soluble form (sHEL-Dbl-Tg mice). The factors responsible for determining the fate of these B cells after encounter with self-antigen were investigated using a cell-tracking technique in which anti-HEL Ig-Tg spleen cells were labeled with the intracellular dye 5-carboxyfluorescein diacetate-succinimidyl ester (CFSE) and injected either into non-Tg recipients or a variety of HEL-Tg hosts. In non-Tg recipients, HEL-binding B cells persisted in the circulation and could be detected in the follicles of the spleen for at least 5 d. On transfer into either mHEL-Tg or sHEL-Tg hosts, they underwent activation and then rapidly disappeared from the blood and spleen over the next 3 d, consistent with the short life span reported previously. Immunohistology of spleens from sHEL-Tg recipients indicated that the transferred B cells had migrated to the outer margins of the periarteriolar lymphoid sheath (PALS), where they were detectable for 24 h before being lost. The positioning of B cells in the outer PALS depended on a critical threshold of Ig receptor binding corresponding to a serum HEL concentration between 0.5 and 15 ng/ml, but was not restricted to endogenously expressed HEL in that the same migratory pattern was observed after transfer into non-Tg recipients given exogenous (foreign) HEL. Moreover, bone marrow-derived immature Ig-Tg B cells homed to the outer PALS of sHEL-Tg mice and then disappeared at the same rate as mature B cells, indicating that the stage of maturation did not influence the fate of self-reactive B cells in a tolerant environment. On the other hand, HEL-binding B cells transferred into sHEL-Dbl-Tg recipients persisted over the 3-d period of study, apparently due to insufficient availability of antigen, as indicated by the fact that the degree of Ig receptor downregulation on the transferred B cells was much less than in sHEL-Tg recipients. If T cell help was provided to Ig-Tg B cells at the time of transfer into sHEL-Tg recipients in the form of preactivated CD4+ T cells specific for major histocompatibility complex-peptide complexes on the B cell surface, HEL-binding B cells migrated through the outer PALS of the spleen to the follicle, where they formed germinal centers, or to adjacent red pulp, where they formed proliferative foci and secreted significant amounts of anti-HEL antibody. Taken together, these results indicated that the outcome of the interaction between self-antigen and B cells is largely determined by a combination of the degree of receptor engagement and availability of T cell help.

scholarly journals Outer Periarteriolar Lymphoid Sheath Arrest and Subsequent Differentiation of Both Naive and Tolerant Immunoglobulin Transgenic B Cells Is Determined by B Cell Receptor Occupancy

1997 ◽  
Vol 186 (5) ◽  
pp. 631-643 ◽  
Author(s):  
Matthew C. Cook ◽  
Antony Basten ◽  
Barbara Fazekas de St. Groth
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Receptor Occupancy ◽  
Cell Receptor ◽  
Antigen Concentration ◽  
Identical Manner ◽  
T Cell Help ◽  
Self Antigen

T-dependent B cell responses in the spleen are initiated in the outer periarteriolar lymphoid sheath (PALS) and culminate in the generation of proliferative foci and germinal center reactions. By pulsing anti–hen egg lysozyme (HEL) immunoglobulin transgenic (IgTg) B cells with various concentrations of HEL in vitro before adoptive transfer into normal recipients, it was shown that a critical number of B cell receptors (BCRs) must be ligated for B cells to undergo arrest in the outer PALS. T cell help was manipulated independently of the BCR stimulus by incubating B cells expressing the appropriate major histocompatibility complex class II antigen with a peptide recognized by CD4+ TCR Tg T cells. B cells which either failed to arrest in the outer PALS due to a subthreshold BCR stimulus, or arrested only transiently due to the brevity of the BCR stimulus, underwent an abortive response within the follicles when provided with T cell help. In contrast, naive B cells stimulated by a sustained, suprathreshold concentration of either foreign or self-antigen and given T cell help, proliferated in the outer PALS and then differentiated. Outer PALS arrest was not influenced by the nature of the B cells occupying the follicle, but appeared to be determined solely by the magnitude of BCR stimulation. Thus antigen-pulsed B cells arrested in the outer PALS in an identical manner irrespective of whether the follicles comprised a population of normal B cells with multiple specificities, a monoclonal naive population, or a monoclonal population of tolerant B cells. In addition, tolerant B cells were found to relocate from the follicles to the outer PALS of HEL/anti-HEL double Tg mice in which the concentration of soluble self-antigen had been increased by zinc feeding. Similarly, when anti-HEL Tg mice were crossed with a second HEL Tg strain expressing a higher concentration of soluble HEL, the tolerant anti-HEL Tg B cells were located constitutively in the outer PALS. Thus, subtle variations in antigen concentration resulted in dramatic changes in positioning of B cells within the spleen. A series of mixed bone marrow chimeras in which the effective antigen concentration was inversely related to the number of self-reactive B cells due to absorption of antigen by transgene-encoded membrane and secreted Ig, was used to confirm that alteration in B cell position previously attributed to changes in follicular composition could be explained on the basis of available antigen concentration, rather than the diversity of the repertoire.

scholarly journals Virus-Induced Maturation and Activation of Autoreactive Memory B Cells

2000 ◽  
Vol 192 (12) ◽  
pp. 1763-1774 ◽  
Author(s):  
Amy J. Reed ◽  
Michael P. Riley ◽  
Andrew J. Caton
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
B Cells ◽  
Cell Receptor ◽  
Primary Response ◽  
Memory B Cells ◽  
Specific Memory ◽  
T Cell Help ◽  
Self Antigen ◽  
Antibody Secreting Cells

We have examined B cell populations that participate in distinct phases of the immune response to the influenza virus A/PR/8/34 hemagglutinin (HA) for their susceptibility to negative selection in mice that express the HA as a neo–self-antigen (HA104 mice). We demonstrated previously that specificity for the neo–self-HA causes a population of immunoglobulin G antibody-secreting cells, which dominate the primary response to virus immunization in BALB/c mice, to be negatively selected in HA104 mice. We find here that in contrast to these primary response B cells, HA-specific memory response B cells developed equivalently in HA104 and nontransgenic (BALB/c) mice. Indeed, there was no indication that HA-specific B cells were negatively selected during memory formation in influenza virus–immunized HA104 mice, even though the neo–self-HA can be recognized by memory B cells. Furthermore, HA-specific autoantibodies were induced in the absence of virus immunization by mating HA104 mice with mice transgenic for a CD4+ HA-specific T cell receptor. These findings indicate that specificity for a self-antigen does not prevent the maturation of autoreactive B cells in the germinal center pathway. Rather, the availability of CD4+ T cell help may play a crucial role in regulating autoantibody responses to the HA in HA104 mice.

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 Arachidonate 5-Lipoxygenase Establishes Adaptive Humoral Immunity by Controlling Primary B Cells and Their Cognate T-Cell Help

2011 ◽  
Vol 178 (1) ◽  
pp. 222-232 ◽  
Author(s):  
Tsutomu Nagashima ◽  
Shingo Ichimiya ◽  
Tomoki Kikuchi ◽  
Yoshiyuki Saito ◽  
Hiroshi Matsumiya ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Humoral Immunity ◽  
T Cell Help

Media ownership and market structures: banes of news media sustainability in Nigeria?

2018 ◽  
Vol 40 (8) ◽  
pp. 1270-1280
Author(s):  
Tokunbo Ojo
Keyword(s):  
Adverse Effects ◽  
Life Span ◽  
News Media ◽  
Media Industry ◽  
Media Ownership ◽  
Short Life ◽  
Market Structures ◽  
Short Life Span ◽  
Democratic Norms ◽  
Privately Owned

With the mixture of government-owned media outlets and private media establishments, Nigerian news media industry is deemed as one of the leading media industries in Africa. But, in spite of its leading status on the continent, the industry is plagued with a series of multi-faceted challenges of sustainability that is rooted in the socio-economic and political contexts. Consequently, privately owned media outlets have short-life span in Nigeria. This article assesses the challenges of news media sustainability in Nigeria. The article underscores the adverse effects of structural deficit in the democratic norms and institutional capabilities on the news media sustainability in Nigeria.

scholarly journals Single Round of Antigen Receptor Signaling Programs Naive B Cells to Receive T Cell Help

Immunity ◽  
2010 ◽  
Vol 32 (3) ◽  
pp. 355-366 ◽  
Author(s):  
Bazarragchaa Damdinsuren ◽  
Yongqing Zhang ◽  
Ashraf Khalil ◽  
William H. Wood ◽  
Kevin G. Becker ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Antigen Receptor ◽  
Receptor Signaling ◽  
Antigen Receptor Signaling ◽  
T Cell Help ◽  
To Receive

scholarly journals Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell help

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Ting-ting Zhang ◽  
David G Gonzalez ◽  
Christine M Cote ◽  
Steven M Kerfoot ◽  
Shaoli Deng ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
B Cell Differentiation ◽  
B Cell Maturation ◽  
Germinal Center B Cell ◽  
T Cell Help ◽  
Dose Dependent

To reconcile conflicting reports on the role of CD40 signaling in germinal center (GC) formation, we examined the earliest stages of murine GC B cell differentiation. Peri-follicular GC precursors first expressed intermediate levels of BCL6 while co-expressing the transcription factors RelB and IRF4, the latter known to repress Bcl6 transcription. Transition of GC precursors to the BCL6hi follicular state was associated with cell division, although the number of required cell divisions was immunogen dose dependent. Potentiating T cell help or CD40 signaling in these GC precursors actively repressed GC B cell maturation and diverted their fate towards plasmablast differentiation, whereas depletion of CD4+ T cells promoted this initial transition. Thus while CD40 signaling in B cells is necessary to generate the immediate precursors of GC B cells, transition to the BCL6hi follicular state is promoted by a regional and transient diminution of T cell help.

Afterword

2020 ◽  
pp. 551-562
Author(s):  
Alberto Mora
Keyword(s):  
Life Span ◽  
National Interest ◽  
Executive Order ◽  
Short Life ◽  
Short Life Span ◽  
Interrogation Technique ◽  
The U.S

The U.S. policy to adopt torture1 as an interrogation technique after the 9/11 attacks had a relatively short life span, yet it was deeply corrosive to the national interest and continues to be.2 First adopted by the administration of President George W. Bush in the summer of 2002, it was formally terminated by an executive order signed by President Barrack Obama on January 22, 2009, his second day in office. The actual official ...

scholarly journals Myeloid and CD4 T Cells Comprise the Latent Reservoir in Antiretroviral Therapy-Suppressed SIVmac251-Infected Macaques

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Celina M. Abreu ◽  
Rebecca T. Veenhuis ◽  
Claudia R. Avalos ◽  
Shelby Graham ◽  
Daymond R. Parrilla ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Life Span ◽  
Latent Reservoir ◽  
Viral Rebound ◽  
Hiv Cure ◽  
Short Life ◽  
Short Life Span ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus (HIV) eradication or long-term suppression in the absence of antiretroviral therapy (ART) requires an understanding of all viral reservoirs that could contribute to viral rebound after ART interruption. CD4 T cells (CD4s) are recognized as the predominant reservoir in HIV type 1 (HIV-1)-infected individuals. However, macrophages are also infected by HIV-1 and simian immunodeficiency virus (SIV) during acute infection and may persist throughout ART, contributing to the size of the latent reservoir. We sought to determine whether tissue macrophages contribute to the SIVmac251 reservoir in suppressed macaques. Using cell-specific quantitative viral outgrowth assays (CD4-QVOA and MΦ-QVOA), we measured functional latent reservoirs in CD4s and macrophages in ART-suppressed SIVmac251-infected macaques. Spleen, lung, and brain in all suppressed animals contained latently infected macrophages, undetectable or low-level SIV RNA, and detectable SIV DNA. Silent viral genomes with potential for reactivation and viral spread were also identified in blood monocytes, although these cells might not be considered reservoirs due to their short life span. Additionally, virus produced in the MΦ-QVOA was capable of infecting healthy activated CD4s. Our results strongly suggest that functional latent reservoirs in CD4s and macrophages can contribute to viral rebound and reestablishment of productive infection after ART interruption. These findings should be considered in the design and implementation of future HIV cure strategies. IMPORTANCE This study provides further evidence that the latent reservoir is comprised of both CD4+ T cells and myeloid cells. The data presented here suggest that CD4+ T cells and macrophages found throughout tissues in the body can contain replication-competent SIV and contribute to rebound of the virus after treatment interruption. Additionally, we have shown that monocytes in blood contain latent virus and, though not considered a reservoir themselves due to their short life span, could contribute to the size of the latent reservoir upon entering the tissue and differentiating into long-lived macrophages. These new insights into the size and location of the SIV reservoir using a model that is heavily studied in the HIV field could have great implications for HIV-infected individuals and should be taken into consideration with the development of future HIV cure strategies.

The Social and Genetic Structure of a Natural Colony of House Mice, Mus musculus, at Healesville WildlifeSanctuary

1983 ◽  
Vol 31 (2) ◽  
pp. 155 ◽  
Author(s):  
GR Singleton
Keyword(s):  
Genetic Structure ◽  
Life Span ◽  
Social Organization ◽  
Turnover Rate ◽  
Spatial Organization ◽  
House Mice ◽  
Genetic Composition ◽  
Short Life ◽  
Short Life Span ◽  
The Social

A 2-year program monitored the spatial organization, genetic structure and turnover rate of an unconfined commensal colony of mice. Four demes (social breeding units) were identified; each usually consisted of one or two males and two or three females. Demes were detected simultaneously in adjoining cages of an aviary (one deme per cage). Movement between demes was rare and the life span of a deme ranged from 2 to 7 months. The adult members of each deme had genotypes compatible to the majority of the young captured in the respective cage of the aviary at the time of residence of the deme. Taken in isolation, these results suggest that social behaviour would have a major impact on the genetic structure of the aviary population. When viewed over the main breeding season, the short life span of a deme and the genetic differences between demes indicate that social organization probably had only a temporary effect on the genetic composition of the aviary population.

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