Absence of interleukin-4 enhances germinal center reaction in secondary immune response

Andoh, A; Masuda, Arata; Yamakawa, Mitsunori; Kumazawa, Yoshio; Kasajima, Takeshi

doi:10.1016/s0165-2478(00)00202-9

Cited by 15 publications

(12 citation statements)

References 23 publications

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“…In vitro studies have indicated that IL-4 is a growth factor promoting GC B-cell differentiation into memory B cells, 25 whereas in vivo studies have demonstrated that the absence of IL-4 enhances the GC reaction in secondary immune responses. 26 HGAL expression in memory B cells, though at lower levels than in GC lymphocytes, provides indirect support for the involvement of HGAL in the differentiation from GC to memory B cells.…”

Section: Discussionmentioning

confidence: 94%

HGAL is a novel interleukin-4–inducible gene that strongly predicts survival in diffuse large B-cell lymphoma

Lossos

Alizadeh

Rajapaksa

et al. 2003

Blood

118

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Section: Discussionmentioning

confidence: 94%

HGAL is a novel interleukin-4–inducible gene that strongly predicts survival in diffuse large B-cell lymphoma

Lossos

Alizadeh

Rajapaksa

et al. 2003

Blood

118

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“…Cytokines, particularly IL-4, -5, -6, -10, and -13 Th2 cytokines are also important for B cell proliferation and class switching. IL-4 is critical for GC formation in Peyer's patches (2), but not for secondary GC in lymph nodes (3).…”

Section: G Erminal Centers (Gc)mentioning

confidence: 99%

Cutting Edge: Critical Role of Inducible Costimulator in Germinal Center Reactions

Dong

Temann

Flavell

2001

The Journal of Immunology

191

138

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Inducible costimulator (ICOS) is a new member of the CD28/CTLA-4 family that is expressed on activated and germinal center (GC) T cells. Recently, we reported that ICOS-deficient mice exhibited profound defects in T cell activation and effector function. Ab responses in a T-dependent primary reaction and in a murine asthma model were also diminished. In the current study, we investigate the mechanism by which ICOS regulates humoral immunity and examine B cell GC reactions in the absence of ICOS. We found that ICOS−/− mice, when immunized with SRBC, had smaller GCs. Furthermore, IgG1 class switching in the GCs was impaired. Remarkably, GC formation in response to a secondary recall challenge was completely absent in ICOS knockout mice. These data establish a critical role of ICOS in regulation of humoral immunity.

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“…IL-4 is a cytokine that is important for the growth and differentiation of Th2 cells. IL-4 is required for GC formation in Peyer's patches, but is dispensable for GC formation in lymph nodes (51,52). Whether These data provide a molecular framework for Cbl-b/Vav1-dependent and Cbl-b/Vav1-independent CD28 activation pathways essential for the organization of secondary lymphoid tissues and in vivo immunity to viral infections.…”

Section: Discussionmentioning

confidence: 96%

Differential Control of CD28-Regulated In Vivo Immunity by the E3 Ligase Cbl-b

Krawczyk

Jones

Atfield

et al. 2005

The Journal of Immunology

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The E3 ubiquitin ligase Casitas B cell lymphoma-b (Cbl-b) plays a critical role in the development of autoimmunity and sets the threshold for T cell activation. In the absence of Cbl-b, T cells stimulated via the TCR respond similarly to those that have received a CD28-mediated costimulatory signal, suggesting that the absence of Cbl-b substitutes for CD28-mediated costimulation. In this study, we show that loss of Cbl-b restores Ig class switching and germinal center formation in Vav1 mutant mice in response to an in vivo viral challenge. Genetic inactivation of Cbl-b also rescues impaired antiviral IgG production in CD28-mutant mice. Moreover, loss of CD28 results in disorganization of follicular dendritic cell clusters, which is also rescued by the Cbl-b mutation. Intriguingly, despite restored antiviral in vivo immunity and follicular dendritic cell clusters, loss of Cbl-b did not rescue germinal center formation in CD28-deficient mice. Mechanistically, in vivo vesicular stomatitis virus-induced IL-4 and IFN-γ production and up-regulation of the inducible costimulatory molecule ICOS were dependent on CD28, and could not be rescued by the loss of Cbl-b. These data provide genetic evidence that CD28-dependent in vivo immune responses and Ig class switching can be genetically uncoupled from germinal center formation and ICOS induction by Cbl-b-Vav1-regulated signaling pathways.

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Absence of interleukin-4 enhances germinal center reaction in secondary immune response

Cited by 15 publications

References 23 publications

HGAL is a novel interleukin-4–inducible gene that strongly predicts survival in diffuse large B-cell lymphoma

HGAL is a novel interleukin-4–inducible gene that strongly predicts survival in diffuse large B-cell lymphoma

Cutting Edge: Critical Role of Inducible Costimulator in Germinal Center Reactions

Differential Control of CD28-Regulated In Vivo Immunity by the E3 Ligase Cbl-b

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