Microarray Analysis of Lyn-Deficient B Cells Reveals Germinal Center-Associated Nuclear Protein and Other Genes Associated with the Lymphoid Germinal Center

Zeljka Korade Mirnics, Eva Caudell, Yan Hua Gao, Kazuhiko Kuwahara, Nobuo Sakaguchi, Tomohiro Kurosaki, Joan Burnside, Károly Mirnics, Seth J. Corey

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Lyn is the only member of the Src family expressed in DT40 B cells, which provide a unique model to study the singular contribution of this protein tyrosine kinase (PTK) family to cell signaling. In these cells, gene ablation of Lyn leads to defective B cell receptor signaling. Complementary DNA array analysis of Lyn-deficient DT40 cells shows that the absence of Lyn leads to down-regulation of numerous genes encoding proteins involved in B cell receptor signaling, proliferation, control of transcription, immunity/inflammation response, and cytoskeletal organization. Most of these expression changes have not been previously associated with Lyn PTK signaling. They include alterations in mRNA levels of germinal center-associated nuclear protein (germinal center-associated DNA primase) (GANP), CD74, CD22, NF-κB, elongation factor 1α, CD79b, octamer binding factor 1, Ig H chain, stathmin, and γ-actin. Changes in GANP expression were also confirmed in Lyn-deficient mice, suggesting that Lyn PTK has a unique function not compensated for by other Src kinases. Because Lyn-deficient mice have impaired development of germinal centers in spleen, the decreased expression of GANP in the Lyn-deficient DT40 cell line and Lyn-deficient mice suggests that Lyn controls the formation and proliferation of germinal centers via GANP. GANP promoter activity was higher in wild-type vs Lyn-deficient cells. Mutation of the PU.1 binding site reduced activity in wild-type cells and had no effect in Lyn-deficient cells. The presence of Lyn enhanced PU.1 expression in a Northern blot. Thus, the following new signaling pathway has been described: Lyn→PU.1→GANP.

Original languageEnglish (US)
Pages (from-to)4133-4141
Number of pages9
JournalJournal of Immunology
Volume172
Issue number7
DOIs
StatePublished - Apr 1 2004

Fingerprint

Germinal Center
Microarray Analysis
Nuclear Proteins
B-Lymphocytes
Genes
Stathmin
DNA Primase
Peptide Elongation Factor 1
src-Family Kinases
Oligonucleotide Array Sequence Analysis
Northern Blotting
Protein-Tyrosine Kinases
Actins
Immunity
Down-Regulation
Spleen
Complementary DNA
Binding Sites
Inflammation
Cell Line

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Microarray Analysis of Lyn-Deficient B Cells Reveals Germinal Center-Associated Nuclear Protein and Other Genes Associated with the Lymphoid Germinal Center. / Mirnics, Zeljka Korade; Caudell, Eva; Gao, Yan Hua; Kuwahara, Kazuhiko; Sakaguchi, Nobuo; Kurosaki, Tomohiro; Burnside, Joan; Mirnics, Károly; Corey, Seth J.

In: Journal of Immunology, Vol. 172, No. 7, 01.04.2004, p. 4133-4141.

Research output: Contribution to journalArticle

Mirnics, Zeljka Korade ; Caudell, Eva ; Gao, Yan Hua ; Kuwahara, Kazuhiko ; Sakaguchi, Nobuo ; Kurosaki, Tomohiro ; Burnside, Joan ; Mirnics, Károly ; Corey, Seth J. / Microarray Analysis of Lyn-Deficient B Cells Reveals Germinal Center-Associated Nuclear Protein and Other Genes Associated with the Lymphoid Germinal Center. In: Journal of Immunology. 2004 ; Vol. 172, No. 7. pp. 4133-4141.
@article{ebe5a96c457248978fc6f2c1969ea20f,
title = "Microarray Analysis of Lyn-Deficient B Cells Reveals Germinal Center-Associated Nuclear Protein and Other Genes Associated with the Lymphoid Germinal Center",
abstract = "Lyn is the only member of the Src family expressed in DT40 B cells, which provide a unique model to study the singular contribution of this protein tyrosine kinase (PTK) family to cell signaling. In these cells, gene ablation of Lyn leads to defective B cell receptor signaling. Complementary DNA array analysis of Lyn-deficient DT40 cells shows that the absence of Lyn leads to down-regulation of numerous genes encoding proteins involved in B cell receptor signaling, proliferation, control of transcription, immunity/inflammation response, and cytoskeletal organization. Most of these expression changes have not been previously associated with Lyn PTK signaling. They include alterations in mRNA levels of germinal center-associated nuclear protein (germinal center-associated DNA primase) (GANP), CD74, CD22, NF-κB, elongation factor 1α, CD79b, octamer binding factor 1, Ig H chain, stathmin, and γ-actin. Changes in GANP expression were also confirmed in Lyn-deficient mice, suggesting that Lyn PTK has a unique function not compensated for by other Src kinases. Because Lyn-deficient mice have impaired development of germinal centers in spleen, the decreased expression of GANP in the Lyn-deficient DT40 cell line and Lyn-deficient mice suggests that Lyn controls the formation and proliferation of germinal centers via GANP. GANP promoter activity was higher in wild-type vs Lyn-deficient cells. Mutation of the PU.1 binding site reduced activity in wild-type cells and had no effect in Lyn-deficient cells. The presence of Lyn enhanced PU.1 expression in a Northern blot. Thus, the following new signaling pathway has been described: Lyn→PU.1→GANP.",
author = "Mirnics, {Zeljka Korade} and Eva Caudell and Gao, {Yan Hua} and Kazuhiko Kuwahara and Nobuo Sakaguchi and Tomohiro Kurosaki and Joan Burnside and K{\'a}roly Mirnics and Corey, {Seth J.}",
year = "2004",
month = "4",
day = "1",
doi = "10.4049/jimmunol.172.7.4133",
language = "English (US)",
volume = "172",
pages = "4133--4141",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "7",

}

TY - JOUR

T1 - Microarray Analysis of Lyn-Deficient B Cells Reveals Germinal Center-Associated Nuclear Protein and Other Genes Associated with the Lymphoid Germinal Center

AU - Mirnics, Zeljka Korade

AU - Caudell, Eva

AU - Gao, Yan Hua

AU - Kuwahara, Kazuhiko

AU - Sakaguchi, Nobuo

AU - Kurosaki, Tomohiro

AU - Burnside, Joan

AU - Mirnics, Károly

AU - Corey, Seth J.

PY - 2004/4/1

Y1 - 2004/4/1

N2 - Lyn is the only member of the Src family expressed in DT40 B cells, which provide a unique model to study the singular contribution of this protein tyrosine kinase (PTK) family to cell signaling. In these cells, gene ablation of Lyn leads to defective B cell receptor signaling. Complementary DNA array analysis of Lyn-deficient DT40 cells shows that the absence of Lyn leads to down-regulation of numerous genes encoding proteins involved in B cell receptor signaling, proliferation, control of transcription, immunity/inflammation response, and cytoskeletal organization. Most of these expression changes have not been previously associated with Lyn PTK signaling. They include alterations in mRNA levels of germinal center-associated nuclear protein (germinal center-associated DNA primase) (GANP), CD74, CD22, NF-κB, elongation factor 1α, CD79b, octamer binding factor 1, Ig H chain, stathmin, and γ-actin. Changes in GANP expression were also confirmed in Lyn-deficient mice, suggesting that Lyn PTK has a unique function not compensated for by other Src kinases. Because Lyn-deficient mice have impaired development of germinal centers in spleen, the decreased expression of GANP in the Lyn-deficient DT40 cell line and Lyn-deficient mice suggests that Lyn controls the formation and proliferation of germinal centers via GANP. GANP promoter activity was higher in wild-type vs Lyn-deficient cells. Mutation of the PU.1 binding site reduced activity in wild-type cells and had no effect in Lyn-deficient cells. The presence of Lyn enhanced PU.1 expression in a Northern blot. Thus, the following new signaling pathway has been described: Lyn→PU.1→GANP.

AB - Lyn is the only member of the Src family expressed in DT40 B cells, which provide a unique model to study the singular contribution of this protein tyrosine kinase (PTK) family to cell signaling. In these cells, gene ablation of Lyn leads to defective B cell receptor signaling. Complementary DNA array analysis of Lyn-deficient DT40 cells shows that the absence of Lyn leads to down-regulation of numerous genes encoding proteins involved in B cell receptor signaling, proliferation, control of transcription, immunity/inflammation response, and cytoskeletal organization. Most of these expression changes have not been previously associated with Lyn PTK signaling. They include alterations in mRNA levels of germinal center-associated nuclear protein (germinal center-associated DNA primase) (GANP), CD74, CD22, NF-κB, elongation factor 1α, CD79b, octamer binding factor 1, Ig H chain, stathmin, and γ-actin. Changes in GANP expression were also confirmed in Lyn-deficient mice, suggesting that Lyn PTK has a unique function not compensated for by other Src kinases. Because Lyn-deficient mice have impaired development of germinal centers in spleen, the decreased expression of GANP in the Lyn-deficient DT40 cell line and Lyn-deficient mice suggests that Lyn controls the formation and proliferation of germinal centers via GANP. GANP promoter activity was higher in wild-type vs Lyn-deficient cells. Mutation of the PU.1 binding site reduced activity in wild-type cells and had no effect in Lyn-deficient cells. The presence of Lyn enhanced PU.1 expression in a Northern blot. Thus, the following new signaling pathway has been described: Lyn→PU.1→GANP.

UR - http://www.scopus.com/inward/record.url?scp=1642406240&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1642406240&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.172.7.4133

DO - 10.4049/jimmunol.172.7.4133

M3 - Article

C2 - 15034025

AN - SCOPUS:1642406240

VL - 172

SP - 4133

EP - 4141

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 7

ER -