Tissue-specific expression of the human CD19 gene in transgenic mice inhibits antigen-independent B-lymphocyte development

Liang-Ji Zhou; Heidi M Smith; Thomas J Waldschmidt; Roland Schwarting; John Daley; Thomas F Tedder

doi:10.1128/mcb.14.6.3884-3894.1994

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Tissue-specific expression of the human CD19 gene in transgenic mice inhibits antigen-independent B-lymphocyte development

Journal article

Open access

Peer reviewed

Tissue-specific expression of the human CD19 gene in transgenic mice inhibits antigen-independent B-lymphocyte development

Liang-Ji Zhou, Heidi M Smith, Thomas J Waldschmidt, Roland Schwarting, John Daley and Thomas F Tedder

Molecular and cellular biology, Vol.14(6), pp.3884-3894

06/1994

DOI: 10.1128/mcb.14.6.3884-3894.1994

PMCID: PMC358755

PMID: 7515149

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https://www.ncbi.nlm.nih.gov/pmc/articles/358755View

Open Access

Abstract

CD19 is a B-cell-specific member of the immunoglobulin superfamily expressed from early pre-B-cell development until plasma cell differentiation. In vitro studies demonstrate that the CD19 signal transduction molecule can serve as a costimulatory molecule for activation through other B-lymphocyte cell surface molecules. However, much remains to be known regarding how CD19 functions in vivo and whether CD19 has different roles at particular stages of B-cell differentiation. Therefore, transgenic mice overexpressing the human CD19 (hCD19) gene were generated to determine whether this transgene would be expressed in a B-lineage-specific fashion and to dissect the in vivo role of CD19 in B-cell development and activation. Expression of the human transgene product was specifically restricted to all B-lineage cells and appeared early in development as occurs with hCD19. In addition, expression of hCD19 severely impaired the development of immature B cells in the bone marrow, with dramatically fewer B cells found in the spleen, peripheral circulation, and peritoneal cavity. The level of hCD19 expressed on the cell surface correlated directly with the severity of the defect in different transgenic lines. These results demonstrate that the hCD19 gene is expressed in a lineage-specific fashion in mice, indicating that the hCD19 gene may be useful for mediating B-lineage-specific expression of other transgene products. In addition, these results indicate an important role for the lineage-specific CD19 molecule during early B-cell development before antigen-dependent activation.

Flow Cytometry

Immunohistochemistry

Signal Transduction

Bone Marrow - immunology

Spleen - immunology

Antigens, CD - biosynthesis

Humans

Male

Antigens, CD - genetics

Restriction Mapping

Aging - immunology

Female

Antigens, Differentiation, B-Lymphocyte - genetics

B-Lymphocytes - cytology

Mice, Inbred C57BL

Mice, Transgenic

Antibodies, Monoclonal

Lymph Nodes - immunology

Organ Specificity

Homozygote

Animals

B-Lymphocytes - immunology

Immunoglobulin M - blood

Antigens, Differentiation, B-Lymphocyte - biosynthesis

Antigens, CD19

Mice

Genetic Carrier Screening

Crosses, Genetic

Details

Title: Subtitle: Tissue-specific expression of the human CD19 gene in transgenic mice inhibits antigen-independent B-lymphocyte development
Creators: Liang-Ji Zhou - Dana-Farber Cancer Institute
Heidi M Smith
Thomas J Waldschmidt
Roland Schwarting
John Daley
Thomas F Tedder
Resource Type: Journal article
Publication Details: Molecular and cellular biology, Vol.14(6), pp.3884-3894
DOI: 10.1128/mcb.14.6.3884-3894.1994
PMID: 7515149
PMCID: PMC358755
NLM abbreviation: Mol Cell Biol
ISSN: 0270-7306
eISSN: 1098-5549
Publisher: United States
Grant note: CA-34183 / NCI NIH HHS AI-26872 / NIAID NIH HHS CA-26872 / NCI NIH HHS
Language: English
Date published: 06/1994
Academic Unit: Pathology
Record Identifier: 9984046815202771

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