Interleukin 5 and interleukin 2 cooperate with interleukin 4 to induce IgG1 secretion from anti-Ig-treated B cells.

Purkerson, Jeffrey M.; Newberg, Michael H.; Wise, George S.; Lynch, Kevin R.; Isakson, Peter C.

doi:10.1084/jem.168.3.1175

Cited by 29 publications

(10 citation statements)

References 9 publications

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“…Cross-reactivity of mouse-reactive detection antibodies with rat IgG precluded attributing the lower IgG1 response in CD1d Ϫ/Ϫ cultures specifically to IL-4 and IL-5. However, the link between IL-4 and IgG1 responses is well established [32,38].…”

Section: Discussionmentioning

confidence: 99%

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Type II NKT cells facilitate Alum-sensing and humoral immunity

Shah

Devera

Rampuria

et al. 2012

Journal of Leukocyte Biology

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Alum-based adjuvants facilitate vaccine-driven humoral immunity, but their mechanism of action remains poorly understood. Herein, we report that lack of type II NKT cells is associated with intact, mature B cells but dampened humoral immunity following immunization with Alum-adsorbed T-dependent antigen. Type II NKT cells facilitated production of IL-4, IL-5, IL-10, IL-13, and antibody by LN and splenocyte cultures following Alum/antigen administration in vivo and antigen restimulation in vitro. Addition of IL-4 and IL-5 to type II NKT-deficient cultures restored in vitro antibody production. Intracellular staining revealed that Alum-primed type II NKT cells coordinated IL-4 secretion by T cells. Alum did not significantly affect CD1d expression in vivo, but addition of CD1d-blocking mAb diminished cytokine production and in vitro antibody production. Type II NKT cells therefore function as part of the Alum-sensing apparatus and in a CD1d-dependent manner, facilitate T(H)2-driven humoral immunity. This may have important consequences for understanding the mechanism of action of Alum-containing vaccines.

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Section: Discussionmentioning

confidence: 99%

“…IL-4, in conjunction with IL-5, is known to drive IgG1 production [32]. We therefore determined whether the cytokine response, shown in Fig.…”

Section: Effect Of T H 2 Cytokines On In Vitro Igg1 Production By Splmentioning

confidence: 99%

Type II NKT cells facilitate Alum-sensing and humoral immunity

Shah

Devera

Rampuria

et al. 2012

Journal of Leukocyte Biology

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“…Conditioned media derived from HeLa cells transfected with the I1,5 cDNA (generously provided by T. Honjo) was also used as a source of ri1,5. EL4 Sn was prepared and depleted of II,4 as described (33).…”

Section: Reagentsmentioning

confidence: 99%

“…In several experimental systems, IL-5 has been shown to enhance secretion of IgG1 and IgE from B cells stimulated with I1,4. I1,5 and -2 promote secretion of IgG1 and IgE from B cells or B lymphoblasts stimulated with LPS and I1,4 (33,34) and from B lymphoblasts treated with a mixture of T cell-derived lymphokines (35). Ib5 enhances secretion of IgE from human PBL stimulated with Ib4 (36,37), and recent studies suggest that I1,5 plays an important role in induction of IgG1 and IgE secretion by murine T,2 clones (29,38).…”

mentioning

confidence: 99%

Interleukin 5 (IL-5) provides a signal that is required in addition to IL-4 for isotype switching to immunoglobulin (Ig) G1 and IgE.

Purkerson

Isakson

1992

The Journal of Experimental Medicine

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SummlryWe have examined the contributions of Interleukin 4 (Ib4), IL-5, and other stimuli to the expression of Immunoglobulin G1 (IgG1) and IgE in murine B lymphoblasts activated with anti-Ig. The combination of IL-4 and -5 induced B lymphobhsts to proliferate and to secrete IgM and IgG1. However, an additional stimulus was required along with II:4 and -5 for induction of IgE secretion. This stimulus was provided by lipopolysaccharides (LPS) or cytokines produced by TC-1 or EL4 cells. In the absence of II.-5, exceptionally high concentrations of II.-4 (>1,000 U/ml) were required to elicit IgG1 and IgE secretion from B lymphoblasts cultured with either LPS or TC-l-conditioned media (CM). To investigate regulation of expression of 3'1 and ~ genes by I1,4, -5, and LPS, the requirements for induction of 3'1 and e germline and productive transcripts were examined. Germline 3'1, but not e, transcripts were detected in RNA from B lymphoblasts treated with I1,4 and -5 for 48 h. In contrast, both germline 3'1 and e transcripts could be detected in B lymphoblasts cultured with I1,4 and LPS, and steady state levels of germline 3'1 transcripts were four-to sevenfold higher in blasts cultured with LPS and Ib4, compared with blasts cultured with I1,4 and -5. LPS enhanced steady state levels of germline transcripts induced by I1,4, but LPS did not promote substantial accumulation of productive 3'1 and e transcripts. In contrast, I1,5 did not affect steady state levels of germline transcripts stimulated by I1,4, but did markedly increase levels of productive 3'1 and e transcripts. Thus, lymphokines regulate two distinct events in isotype switching: induction of germline transcripts (I1,4), and production of VDJ-C3'I and VDJ-Ce mRNA (I1,5), which leads to secretion of IgG1 and IgE.

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“…Induction of switching requires a B-cell activator, such as (i) LPS, (ii) a mimic of a T-cell-independent antigen, such as anti-Ig bound to Sepharose beads or anti-IgDdextran in the presence of IL-5, or (iii) T-cell contact help (48,71,73,88).…”

mentioning

confidence: 99%