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Article ; Online: To B-1 or not to B-1.

Wortis, Henry H

2017 Volume 18, Issue 4, Page(s) 365–366

Language	English
Publishing date	2017-03-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/ni.3715
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Article: The H-2 haplotype of a thymus graft influences the Ir gene regulated IgG3, IgG1, IgG2b, and IgG2a anti-(T,G)-A--L antibody responses of high-responder F1.nude mice.

Press, J L / Haber, J / Wortis, H H

Journal of immunology (Baltimore, Md. : 1950)

1982 Volume 128, Issue 1, Page(s) 441–446

Abstract: In order to examine whether the H-2 haplotype of a thymus graft influences the levels of IgG3, IgG1 ... control, genotypic high-responder (H-2b X H-2k)F1.nude mice were grafted with thymuses from irradiated ... neonatal low-responder (H-2k) or high-responder (H-2b or (H-2k X H-2b)F1) mice and immunized with (T,G ...

Abstract	In order to examine whether the H-2 haplotype of a thymus graft influences the levels of IgG3, IgG1, IgG2b, and IgG2a antibodies produced in an in vivo response to antigens under immune response (Ir) gene control, genotypic high-responder (H-2b X H-2k)F1.nude mice were grafted with thymuses from irradiated, neonatal low-responder (H-2k) or high-responder (H-2b or (H-2k X H-2b)F1) mice and immunized with (T,G)-A--L. All IgG antibody responses to (T,G)-A--L in high-responder mice were shown to be thymus dependent. The majority of F1.nude mice grafted with thymuses from high-responder haplotype donors produced high-responder levels of IgG anti-(T,G)-A--L antibodies. Conversely, the majority of F1.nude mice grafted with thymuses from low-responder haplotype donors gave low-responder phenotypic patterns. The modulation of the Ir gene phenotype was not restricted to a particular IgG isotype, but affected IgG3, IgG1, IgG2b, and IgG2a. The F1 . nude mice grafted with low-responder haplotype thymuses were able to produce IgG1, IgG3, and IgG2b antibodies to sheep erythrocytes, a thymus-dependent (TD) antigen not under overt Ir gene control. Circulating peripheral T cells were shown to be of host origin. By these criteria, the thymus grafts did enable F1.nude mice to respond to a TD antigen. These results support the concept that thymic H-2 determinants are involved in at least the selection of H-2 restricted T cell subsets, if not also the derivation of the T cell receptor repertoire for self and/or antigen recognition.
MeSH term(s)	Animals ; Dose-Response Relationship, Immunologic ; Erythrocytes/immunology ; Genes, MHC Class II ; Genotype ; H-2 Antigens/genetics ; H-2 Antigens/immunology ; Haploidy ; Hybridization, Genetic ; Immunoglobulin G/biosynthesis ; Immunoglobulin G/classification ; Immunoglobulin G/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Nude/genetics ; Peptides/immunology ; Sheep ; T-Lymphocytes/immunology ; Thymus Gland/transplantation
Chemical Substances	H-2 Antigens ; Immunoglobulin G ; Peptides ; (T,G)-A-L (28704-27-0)
Language	English
Publishing date	1982-01
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
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Article ; Online: Mineralocorticoid receptors in immune cells: emerging role in cardiovascular disease.

Bene, Nicholas C / Alcaide, Pilar / Wortis, Henry H / Jaffe, Iris Z

Steroids

2014 Volume 91, Page(s) 38–45

Abstract: Mineralocorticoid receptors (MRs) contribute to the pathophysiology of hypertension and cardiovascular disease in humans. As such, MR antagonists improve cardiovascular outcomes but the molecular mechanisms remain unclear. The actions of the MR in the ... ...

Abstract	Mineralocorticoid receptors (MRs) contribute to the pathophysiology of hypertension and cardiovascular disease in humans. As such, MR antagonists improve cardiovascular outcomes but the molecular mechanisms remain unclear. The actions of the MR in the kidney to increase blood pressure are well known, but the recent identification of MRs in immune cells has led to novel discoveries in the pathogenesis of cardiovascular disease that are reviewed here. MR regulates macrophage activation to the pro-inflammatory M1 phenotype and this process contributes to the pathogenesis of cardiovascular fibrosis in response to hypertension and to outcomes in mouse models of stroke. T lymphocytes have recently been implicated in the development of hypertension and cardiovascular fibrosis in mouse models. MR activation in vivo promotes T lymphocyte differentiation to the pro-inflammatory Th1 and Th17 subsets while decreasing the number of anti-inflammatory T regulatory lymphocytes. The mechanism likely involves activation of MR in antigen presenting dendritic cells that subsequently regulate Th1/Th17 polarization by production of cytokines. Alteration of the balance between T helper and T regulatory lymphocytes contributes to the pathogenesis of hypertension and atherosclerosis and the associated complications. B lymphocytes also express the MR and specific B lymphocyte-derived antibodies modulate the progression of atherosclerosis. However, the role of MR in B lymphocyte function remains to be explored. Overall, recent studies of MR in immune cells have identified new mechanisms by which MR activation may contribute to the pathogenesis of organ damage in patients with cardiovascular risk factors. Conversely, inhibition of leukocyte MR may contribute to the protective effects of MR antagonist drugs in cardiovascular patients. Further understanding of the role of MR in leukocyte function could yield novel drug targets for cardiovascular disease.
MeSH term(s)	Animals ; Cardiovascular Diseases/metabolism ; Humans ; Leukocytes/metabolism ; Models, Biological ; Receptors, Mineralocorticoid/metabolism ; Renin-Angiotensin System
Chemical Substances	Receptors, Mineralocorticoid
Language	English
Publishing date	2014-04-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80312-1
ISSN	1878-5867 ; 0039-128X
ISSN (online)	1878-5867
ISSN	0039-128X
DOI	10.1016/j.steroids.2014.04.005
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Article ; Online: A conserved enhancer element differentially regulates developmental expression of CD5 in B and T cells.

Berland, Robert / Fiering, Steven / Wortis, Henry H

Journal of immunology (Baltimore, Md. : 1950)

2010 Volume 185, Issue 12, Page(s) 7537–7543

Abstract: We previously identified an enhancer element upstream of the mouse cd5 gene that was required in reporter assays for the induction of cd5 promoter activity by BCR cross-linking. This element is highly conserved in placental mammals. To determine its ... ...

Abstract	We previously identified an enhancer element upstream of the mouse cd5 gene that was required in reporter assays for the induction of cd5 promoter activity by BCR cross-linking. This element is highly conserved in placental mammals. To determine its physiological role, we have now generated mice with a targeted deletion of the enhancer. The result is the loss of CD5 expression in peritoneal and splenic B-1a cells of adult mice and an inability to induce CD5 by cross-linking of the BCR on splenic B-2 cells. Surprisingly, CD5 expression on B-1a cells of neonatal mice was only minimally compromised. Cd5 enhancer deletion also had only a modest effect on CD5 expression in the T lineage. Thus, this enhancer provides age- and tissue-specific regulation of CD5 expression and is an example of the utilization of different modes of regulation of expression in T and B cells.
MeSH term(s)	Aging/genetics ; Aging/immunology ; Aging/metabolism ; Animals ; B-Lymphocytes/cytology ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; CD5 Antigens/biosynthesis ; CD5 Antigens/genetics ; CD5 Antigens/immunology ; Enhancer Elements, Genetic/physiology ; Gene Expression Regulation/genetics ; Gene Expression Regulation/immunology ; Immunologic Capping ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Organ Specificity/physiology ; Peritoneal Cavity/cytology ; Receptors, Antigen, B-Cell/genetics ; Receptors, Antigen, B-Cell/immunology ; Receptors, Antigen, B-Cell/metabolism ; Spleen/cytology ; Spleen/immunology ; Spleen/metabolism ; T-Lymphocytes/cytology ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism
Chemical Substances	CD5 Antigens ; Cd5 protein, mouse ; Receptors, Antigen, B-Cell
Language	English
Publishing date	2010-11-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1002173
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Article: THE CONTRIBUTION OF SOCIAL ENVIRONMENT TO THE DEVELOPMENT OF PREMATURE CHILDREN.

WORTIS, H / FREEDMAN, A

The American journal of orthopsychiatry

2003 Volume 35, Page(s) 57–68

MeSH term(s)	Adaptation, Psychological ; African Continental Ancestry Group ; Child ; Education ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Intelligence ; Motor Skills ; Parent-Child Relations ; Psychological Tests ; Social Conditions ; Social Environment
Language	English
Publishing date	2003-09-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	280031-7
ISSN	1939-0025 ; 0002-9432
ISSN (online)	1939-0025
ISSN	0002-9432
DOI	10.1111/j.1939-0025.1965.tb02268.x
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Article: The significance of the phenomenon of extinction.

WORTIS, S B / BENDER, M B / TEUBER, H L

The Journal of nervous and mental disease

2008 Volume 107, Issue 4, Page(s) 382–387

MeSH term(s)	Emotions ; Humans ; Psychology
Language	English
Publishing date	2008-06-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	3020-x
ISSN	1539-736X ; 0022-3018
ISSN (online)	1539-736X
ISSN	0022-3018
DOI	10.1097/00005053-194810740-00007
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Article: Surface markers, heavy chain sequences and B cell lineages.

Wortis, H H

International reviews of immunology

1992 Volume 8, Issue 2-3, Page(s) 235–246

Abstract: A unifying theory of B cell development and lineage commitment is presented. There are two firmly established B lineages: cells which normally arise only from fetal sources and lack N insertions in their rearranged heavy chains; and N-containing cells ... ...

Abstract	A unifying theory of B cell development and lineage commitment is presented. There are two firmly established B lineages: cells which normally arise only from fetal sources and lack N insertions in their rearranged heavy chains; and N-containing cells which arise from adult bone marrow precursors (and perhaps from late fetal sources). Commitment to the expression of CD5 and the capacity for long-life (or self-renewal) are induced as a consequence of sIg cross-linking, typically by a repeating epitope, thymus independent type two antigen. Alternatively, activation resulting from cognate interaction with a helper T cell does not induce CD5 but results in lower expression of J11d. In this case activation occurs in the absence of sIg cross-linking. It is further proposed that differences in the Ig repertoire make it highly likely that fetal/neonatal, but not adult derived B cells will be induced to express CD5. The model offers a plausible explanation for the correlation of CD5 expression and natural autoantibody production by neonatal B cells. Possible sources of pathogenic autoantibody are discussed in the context of this model.
MeSH term(s)	Animals ; Antigens, CD ; Antigens, Differentiation, B-Lymphocyte ; B-Lymphocyte Subsets/immunology ; CD5 Antigens ; Gene Rearrangement, B-Lymphocyte, Heavy Chain ; Genes, Immunoglobulin ; Humans ; Lymphocyte Activation ; Mice ; Models, Biological
Chemical Substances	Antigens, CD ; Antigens, Differentiation, B-Lymphocyte ; CD5 Antigens
Language	English
Publishing date	1992
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	632825-8
ISSN	1545-5858 ; 0883-0185
ISSN (online)	1545-5858
ISSN	0883-0185
DOI	10.3109/08830189209055576
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Article: Normal B-1a cell development requires B cell-intrinsic NFATc1 activity.

Berland, Robert / Wortis, Henry H

Proceedings of the National Academy of Sciences of the United States of America

2003 Volume 100, Issue 23, Page(s) 13459–13464

Abstract: B-1a cells, an anatomically, phenotypically, and functionally distinct subset of B cells that produce the bulk of natural serum IgM and much of gut-associated IgA, are an important component of the early response to pathogens. Because the induced ... ...

Abstract	B-1a cells, an anatomically, phenotypically, and functionally distinct subset of B cells that produce the bulk of natural serum IgM and much of gut-associated IgA, are an important component of the early response to pathogens. Because the induced expression of CD5, a hallmark of B-1a cells, requires a nuclear factor of activated T cells (NFAT)-dependent enhancer, we examined the role of NFAT transcription factors in B-1a development. Here we show that the B-1a compartment is normal in mice lacking NFATc2 but essentially absent in mice lacking NFATc1. Loss of NFATc1 affects both peritoneal and splenic B-1a cells. Because there is a loss of B-1 cells defined by markers other than CD5, NFATc1 is not required simply for CD5 expression on B-1a cells. Using mixed-allotype chimeras and retroviral-mediated gene transduction we show that the requirement for NFATc1 is B cell-intrinsic. We also demonstrate that NFATc1 protein expression is elevated approximately 5-fold in B-1a cells compared with B-2 cells. This is the first definitive demonstration of a B cell-intrinsic function for an NFAT family transcription factor.
MeSH term(s)	Animals ; B-Lymphocytes/cytology ; B-Lymphocytes/pathology ; Blotting, Western ; CD5 Antigens/biosynthesis ; Cell Separation ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/physiology ; Flow Cytometry ; Green Fluorescent Proteins ; Immunoblotting ; Immunoglobulin A/metabolism ; Immunoglobulin M/metabolism ; Liver/embryology ; Liver/metabolism ; Luminescent Proteins/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; NFATC Transcription Factors ; Nuclear Proteins ; Phenotype ; Retroviridae/genetics ; Spleen/cytology ; Transcription Factors/genetics ; Transcription Factors/physiology
Chemical Substances	CD5 Antigens ; DNA-Binding Proteins ; Immunoglobulin A ; Immunoglobulin M ; Luminescent Proteins ; NFATC Transcription Factors ; Nfatc1 protein, mouse ; Nfatc2 protein, mouse ; Nuclear Proteins ; Transcription Factors ; Green Fluorescent Proteins (147336-22-9)
Language	English
Publishing date	2003-11-11
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2233620100
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Article: Cutting edge commentary: origins of B-1 cells.

Wortis, H H / Berland, R

Journal of immunology (Baltimore, Md. : 1950)

2001 Volume 166, Issue 4, Page(s) 2163–2166

Abstract: The origin of B-1a cells, a minority population of B cells that express CD5, are abundant in coelomic cavities, and often produce autoantibodies, has been the subject of study for many years. Accumulating evidence demonstrates that the hypothesis that ... ...

Abstract	The origin of B-1a cells, a minority population of B cells that express CD5, are abundant in coelomic cavities, and often produce autoantibodies, has been the subject of study for many years. Accumulating evidence demonstrates that the hypothesis that only B cells arising in fetal or neonatal tissues have the potential to become B-1a cells cannot be true. Rather, B cell receptor-mediated signaling initiated by ligation of autoantigen has now been shown to be required for induction of the B-1a phenotype. Furthermore, cells with a functional B-1a phenotype can be induced from adult precursors by appropriate Ag. At the same time, microenvironment-specific events may determine the likelihood that a given B cell, either adult or fetal derived, enters this pathway. CD5 expression and possibly localization to the peritoneum appear to provide some protection to autoreactive cells otherwise slated for elimination.
MeSH term(s)	Animals ; B-Lymphocyte Subsets/cytology ; B-Lymphocyte Subsets/immunology ; B-Lymphocyte Subsets/metabolism ; Cell Differentiation/genetics ; Cell Differentiation/immunology ; Cell Lineage/genetics ; Cell Lineage/immunology ; Immunophenotyping
Language	English
Publishing date	2001-01-10
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.166.4.2163
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Article: Origins and functions of B-1 cells with notes on the role of CD5.

Berland, Robert / Wortis, Henry H

Annual review of immunology

2002 Volume 20, Page(s) 253–300

Abstract: Whether B-1a (CD5+) cells are a distinct lineage derived from committed fetal/neonatal precursors or arise from follicular B-2 cells in response to BCR ligation and other, unknown signals remains controversial. Recent evidence indicates that B-1a cells ... ...

Abstract	Whether B-1a (CD5+) cells are a distinct lineage derived from committed fetal/neonatal precursors or arise from follicular B-2 cells in response to BCR ligation and other, unknown signals remains controversial. Recent evidence indicates that B-1a cells can derive from adult precursors expressing an appropriate specificity when the (self-) antigen is present. Antibody specificity determines whether a B cell expressing immunoglobulin transgenes has a B-2, B-1a or marginal zone (MZ) phenotype. MZ cells share many phenotypic characteristics of B-1 cells and, like them, appear to develop in response to T independent type 2 antigens. Because fetal-derived B cell progenitors fail to express terminal deoxynucleotidyl transferase (TdT) and for other reasons, they are likely to express a repertoire that allows selection into the B-1a population. As it is selected by self-antigen, the B-1 repertoire tends to be autoreactive. This potentially dangerous repertoire is also useful, as B-1 cells are essential for resistance to several pathogens and they play an important role in mucosal immunity. The CD5 molecule can function as a negative regulator of BCR signaling that may help prevent inappropriate activation of autoreactive B-1a cells.
MeSH term(s)	Animals ; Autoimmunity ; B-Lymphocyte Subsets/cytology ; B-Lymphocyte Subsets/immunology ; Bone Marrow Cells/cytology ; Bone Marrow Cells/immunology ; CD5 Antigens/chemistry ; CD5 Antigens/genetics ; CD5 Antigens/metabolism ; Cell Differentiation ; Fetus/cytology ; Fetus/immunology ; Humans ; Immunity, Mucosal ; Immunoglobulin A/biosynthesis ; Immunoglobulin M/blood ; Lymphocyte Activation ; Mice ; Phenotype ; Receptors, Antigen, B-Cell/metabolism ; Signal Transduction
Chemical Substances	CD5 Antigens ; Immunoglobulin A ; Immunoglobulin M ; Receptors, Antigen, B-Cell
Language	English
Publishing date	2002
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	604953-9
ISSN	1545-3278 ; 0732-0582
ISSN (online)	1545-3278
ISSN	0732-0582
DOI	10.1146/annurev.immunol.20.100301.064833
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