The Abelson-virus-transformed mouse pre-B-cell line 18-81 switches almost exclusively from
μ to γ2b. From nuclear extracts of this cell line, we have isolated a factor that specifically binds
to Sγ2b. After an eight-step purification scheme, in which different types of DNA-affinity chromatography
were used as key elements, we obtained a preparation with two narrowly spaced
bands at approximately 69 kD on a silver-stained SDS gel. Binding specificity of main-peak
fractions of affinity-purified proteins was analyzed by gel shift assays in which Sγ2b, but not
Sμ, competes. The results are consistent with this factor being part of the switch recombinase.

Heiner Völk

Matthias Wabl

A Protein Binding Specifically to the IgG2b Switch Region

The CD3ɛ and ζ chains of the TCR have been shown to possess independent signaling capabilities.
Studies with chimeric molecules containing the cytoplasmic domains of either ζ or ɛ have
suggested that these two structurally distinct members of the TCR-CD3 complex are able to
function autonomously and have redundant features in the context of TCR-signal transduction
in mature T cells. Expression of a chimeric human IL-2-receptor-ζ-chain molecule in the
CD4+8+ T-cell line, DPK, has enabled us to directly analyze responses initiated by the ζ-chain-signaling
module alone within the context of immature T-cell differentiation. In this paper, we
show that antibody crosslinking of the chimeric ζ chain delivers only a limited activation signal
as measured by Ca[2+] flux, induction of low-level CD5 expression, and minimal differentiation
as assessed by loss of cell-surface CD8 expression. TCR-induced activation through antibody
crosslinking of the endogenous CD3ɛ receptor in the absence of costimulation was also
relatively inefficient in initiating activation and differentiation. However, co-crosslinking of the
CD4 coreceptor with CD3 resulted in a synergistic response, where as there was little effect of
co-crosslinking of CD4 and the ζ-chain chimera. Striking differences were also observed in the
substrate pattern of tyrosine phosphorylation, as well as lymphokine secretion following triggering
through the intact TCR versus the ζ chain alone. These results indicate that although the
ζ-chain may possess some signaling capacities similar to that of the intact TCR, it appears to
have limited function as an autonomous subunit in initiating CD4+8+ T-cell differentiation.

Jenefer Dekoning

Jonathan G. Kaye

Requirements for Differentiation of an Immature CD4+8+ T-Cell Line

It is widely accepted that the thymic microenvironment regulates normal thymopoiesis
through a highly coordinated and complex series of cellular and cytokine interactions. A direct
corollary of this is that abnormalities within the microenvironment could be of etiologic
significance in T-cell-based diseases. Our laboratory has developed a large panel of
monoclonal antibodies (mAbs) that react specifically with epithelial or nonepithelial
markers in the thymus. We have taken advantage of these reagents to characterize the
thymic microenvironment of several genetic strains of mice, including BALB/cJ,
C57BL/6J, NZB/BlnJ, SM/J, NOD/Ltz, NOD/Ltz-scid/sz, C57BL/6J-Hcph<mml:math id="E1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mrow><mml:mi>m</mml:mi><mml:mi>e</mml:mi></mml:mrow></mml:mrow></mml:math>/Hcph<mml:math id="E2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mrow><mml:mi>m</mml:mi><mml:mi>e</mml:mi></mml:mrow></mml:mrow></mml:math>, and
ALY/NscJcl-aly/aly mice, and littermate control animals. We report herein that control
mice, including strains of several backgrounds, have a very consistent phenotypic profile
with this panel of monoclonal antibodies, including reactivity with thymic epithelial cells
in the cortex, the medulla and the corticomedullary junction, and the extracellular matrix.
In contrast, the disease-prone strains studied have unique, abnormal staining of thymic cortex
and medulla at both the structural and cellular levels. These phenotypic data suggest
that abnormalities in interactions between developing thymocytes and stromal cells characterize
disease-prone mice.

Yuichi Takeoka

Shao-Yuan Chen

Richard L. Boyd

Koichi Tsuneyama

Nobuhisa Taguchi

Shinji Morita

Hisashi Yago

Seishi Suehiro

Aftab A. Ansari

Leonard D. Shultz

M. Eric Gershwin

A Comparative Analysis of the Murine Thymic Microenvironment in Normal, Autoimmune, and Immunodeficiency States

In recent years, integrative animal biologists and behavioral scientists have begun to understand
the complex interactions between the immune system and the neuroendocrine system.
Amphibian metamorphosis offers a unique opportunity to study dramatic hormone-driven
changes in the immune system in a compressed time frame. In the South African clawed frog,
Xenopus laevis, the larval pattern of immunity is distinct from that of the adult, and metamorphosis
marks the transition from one pattern to the other. Climax of metamorphosis is
characterized by significant elevations in thyroid hormones, glucocorticoid hormones, and the
pituitary hormones, prolactin and growth hormone. Previously, we and others have shown that
elevated levels of unbound glucocorticoid hormones found at climax of metamorphosis are associated
with a natural decline in lymphocyte numbers, lymphocyte viability, and mitogen-induced
proliferation. Here we present evidence that the mechanism for loss of lymphocytes at
metamorphosis is glucocorticoid-induced apoptosis. Inhibition of lymphocyte function and
loss of lymphocytes in the thymus and spleen are reversible by in vitro or in vivo treatment
with the glucocorticoid receptor antagonist, RU486, whereas the mineralocorticoid receptor
antagonist, RU26752, is poorly effective. These observations support the hypothesis that loss
of larval lymphocytes and changes in lymphocyte function are due to elevated concentrations
of glucocorticoids that remove unnecessary lymphocytes to allow for development of immunological
tolerance to the new adult-specific antigens that appear as a result of metamorphosis.

Louise A. Rollins-Smith

Katherine S. Barker

A. Tray Davis

Involvement of Glucocorticoids in the Reorganization of
the Amphibian Immune System at Metamorphosis

The major histocompatibility complex (MHC) is a cluster of genes encoding products central
to all major functions of the vertebrate immune system. Evidence for an MHC can be found
in all vertebrate groups that have been examined except the jawless fishes. Expression of
MHC class I and class II antigens early in ontogeny is critically important for development
of T lymphocytes capable of discriminating self from nonself. Because of this essential role
in T-cell development, the ontogeny of MHC expression in the South African clawed frog,
Xenopus laevis, was studied. Previous studies of MHC class I expression in Xenopus laevis suggested that class I antigens are virtually absent from tadpole tissues until climax of metamorphosis.
We therefore examined the possible role of thyroid hormones (TH) in the induction
of class I. By flow cytometry, a small amount of class I expression was detectable on
splenocytes and erythrocytes in untreated frogs at prometamorphic stages 55-58, and the
amount increased significantly at the conclusion of metamorphic climax. Thus, metamorphosis
is associated with increased intensity of class I expression. Neither inhibition nor acceleration
of metamorphosis altered the timing of onset of class I expression. However, inhibition
of metamorphosis prevented the increase in class I expression characteristic of adult
cell populations. Because expression was not accelerated in TH-treated frogs or delayed in
metamorphosis-inhibited frogs, it is unlikely that TH are the direct developmental cues that
induce expression, although they seem to be required for the upregulation of class I expression
occurring at metamorphosis. Differences in the pattern of expression in different subpopulations
of cells suggest a complex pattern of regulation of expression of class I antigens
during ontogeny.

Martin F. Flajnik

Patrick J. Blair

Wayne F. Green

Involvement of Thyroid Hormones in the Expression of MHC class I Antigens During Ontogeny in Xenopus

John D. Hansen

Inspection of the 3’ UTR Genomic Region for RAG1 and RAG2 in Rainbow Trout (Oncorhynchus mykiss) Reveals
Potential Regulatory Motifs

During early neonatal life, important changes occur in the gut. The intestine is challenged by
both milk and a microbial flora. Later on, at weaning, the diet of mice changes from milk to
pelleted food leading to changes in microbial contents. This period seems essential for a complete
development of the mucosal immune system. We investigated the development of both
intraepithelial (IEL) and lamina propria lymphocytes (LPL), from day 5, and every 5 days, up
to day 30 after birth. IEL and LPL were isolated from the small intestine and the phenotype
was assessed by FACS analyses, using antibodies for detection of T-cell markers CD3,
TCRαβ, TCRγδ, CD4, CD8α, CD8β, CD5, CD18, CD54, and CD49d. Our data show a clear
increase in the number of LPL just before weaning, while the number of IEL increased after
day 15. A more mature pattern of membrane antigen expression of both IEL and LPL was observed
at weaning. The adhesion molecules CD18, CD54, and CD49d, essential for cellular
communication of lymphocytes, showed an expression peak at weaning. In conclusion, the
mouse mucosal immune system develops during the first 3 weeks of neonatal life leading to
the formation of a more mature immune system at weaning.

Jessica C. A. Ter Steege

Wim A. Buurman

Pierre-Philippe Forget

The Neonatal Development of Intraepithelial and Lamina
Propria Lymphocytes in the Murine Small Intestine

Pro-B cells are early B-cell progenitors that retain macrophage potential. We have studied
MHC class II molecules and invariant chain inducibility on four class II negative mouse pro-
B-cell clones. We analyzed the effects of IL-4 and IFN-γ, which represent the major inducers
of class II in the B-lymphoid and monocytic/macrophage lineages, respectively. After 48 h of
treatment with either cytokine, three pro-B-cell clones (C2.13, A1.5, and F2.2) expressed intracellular
invariant chain and cell-surface class II molecules. One clone (D2.1) remained negative.
As already reported, more differentiated 70Z/3 pre-B cells were inducible by IL-4 only.
These data suggest that the induction of class II and invariant-chain genes are subject to regulation
throughout B-cell differentiation.

Suzanne Lombard-Platet

Valerie Meyer

Rhodri Ceredig

Both IFN-γ and IL-4 Induce MHC Class II Expression at the Surface of Mouse Pro-B Cells

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Journal of Immunology Research provides a platform for scientists and clinicians working in different and diverse areas of immunology and therapy.

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Chief Editor, Professor Holland, has a background focusing on researching the development of conjunctival fibrosis and the characterisation of immune responses to potential C. trachomatis vaccine candidates.

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Journal of Immunology Research - Table of contents 1997

title

Journal of Immunology Research provides a platform for scientists and clinicians working in different and diverse areas of immunology and therapy.

Journal of Immunology Research